|Year : 2010 | Volume
| Issue : 3 | Page : 478-483
|Comparative study of anticoagulation versus saline flushes in continuous renal replacement therapy
Amit P Nagarik, Sachin S Soni, Gopal Kishan Adikey, Anuradha Raman
Department of Nephrology, Mediciti Hospitals, Hyderabad, Andhra Pradesh, India
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|Date of Web Publication||26-Apr-2010|
| Abstract|| |
Systemic heparinization during continuous renal replacement therapy (CRRT) is associated with disadvantage of risk of bleeding. This study analyses the efficacy of frequent saline flushes compared with heparin anticoagulation to maintain filter life. From January 2004 to November 2007, 65 critically ill patients with acute renal failure underwent CRRT. Continuous venovenous hemodialfiltration (CVVHDF) was performed using Diapact Braun CRRT machine. 1.7% P.D. fluid was used as dialysate. 0.9% NS with addition of 10% Ca Gluconate, Magnesium Sulphate, Soda bicarbonate and Potassium Chloride added sequentially in separate units were used for replacement, carefully monitoring their levels. Anticoagulation of extracorporeal circuit was achieved with unfractionated heparin (250-500 units alternate hour) in 35 patients targeting aPTT of 45-55 seconds. No anticoagulation was used in 30 patients with baseline APTT > 55 seconds and extracorporeal circuit was maintained with saline flushes at 30 min interval. 65 patients including 42 males. Co-morbidities were comparable in both groups. HMARF was significantly more common in heparin group while Sepsis was comparable in both the groups. CRRT parameters were similar in both groups. Average filter life in heparin group was 26 ± 6.4 hours while it was 24.5 ± 6.36 hours in heparin free group ( P=NS). Patients receiving heparin had 16 bleeding episodes (0.45/patient) while only four bleeding episodes occurred in heparin free group (0.13/patient, P< 0.05). Mortality was 71% in heparin group and 67% in heparin free group. Frequent saline flushes is an effective mode of maintainance of extracorporeal circuit in CRRT when aPTT is already on the higher side, with significantly decreased bleeding episodes.
|How to cite this article:|
Nagarik AP, Soni SS, Adikey GK, Raman A. Comparative study of anticoagulation versus saline flushes in continuous renal replacement therapy. Saudi J Kidney Dis Transpl 2010;21:478-83
|How to cite this URL:|
Nagarik AP, Soni SS, Adikey GK, Raman A. Comparative study of anticoagulation versus saline flushes in continuous renal replacement therapy. Saudi J Kidney Dis Transpl [serial online] 2010 [cited 2020 Nov 25];21:478-83. Available from: https://www.sjkdt.org/text.asp?2010/21/3/478/62737
| Introduction|| |
Acute Renal Failure (ARF) also referred to as Acute kidney injury is a common complication in an intensive care setting, the incidence varying between 20-50%.  ARF usually presents in the context of Multi Organ Dysfunction Syndrome (MODS).  and is associated with hemodynamic instability and high mortality rates ranging from 25% to 90%. ,,,,,,, Intermittent he modialysis in such patients is associated with concerns regarding hemodynamic stability during dialysis, renal function deterioration and inability to adequately remove solutes and water. Continous Renal Replacement Therapy (CRRT) introduced in 1977  is a significant technical advancement and is currently used in 80% of ARF cases in the ICU setting. 
However CRRT is associated with limitations especially high cost and need for prolonged anticoagulation. Inadequate anticoagulation may lead to increased clotting of the circuit leading to increased costs and excess anticoagulation is associated with increased risk of bleeding. Although, citrate anticoagulation is increasingly being used, unfractionated heparin is the anticoagulant used in almost all the centers in India and majority of the centers worldwide. However, the use of heparin is associated with significant bleeding risks (10-50%)  especially in patients with coagulation disturbances. The aim of this prospective study was to compare the efficacy of isotonic saline flushes with unfractionated heparin to prevent clotting.
| Materials and Methods|| |
Sixty five hemodynamically unstable patients with ARF who received CRRT from January 2005 to November 2007 were prospectively analysed. ARF was defined as:
Baseline demographic parameters like age, gender, comorbidities, etiology of ARF were recorded at the time of initiation of CRRT. Arteriovenous fistula was used as vascular access in four cases: Femoral in 42 cases, IJV in ten and Subclavian in nine cases.
- S. Creatinine > 1.3 mg% with a normal baseline renal function.
- Increase in S. Creatinine > 0.5 mg% whennormal baseline S. Creatinine > 1.3 mg%.
- Return of S. Creatinine to normal when baseline S. Creatinine is not available.
- Hemodynamic instability was defined as systolic blood pressure < 100 mmHg despite 1 or more ionotropic agents.
Continous Veno Venous Hemodiafiltration (CVVHDF) was done in all patients with Diapact Braun CRRT machine. CRRT was initially started at a blood flow rate of 100 mL/min which was gradually increased to a rate of 200 mL/min. Dialysate flow was 1 L/hr. 1.7% peritoneal dialysis fluid or commercially available hemosol BO (Hospal division, Gambro limited) solution was used as dialysate at rate of 1 L/hr. Replacement fluid was given as per institutional protocol which included 0.9% or 0.45% saline with 10 % Ca gluconate, Mg SO4, 7.5% Sodium bicarbonate, Potassium chloride added sequentially as and when necessary. Proctoclysis enema (Sodium phosphate 10%) given through nasogastric tube was used for phosphorous replacement. Replacement fluid was given at a fixed rate of 400 mL/hr by pre-dilution method. Unfractionated heparin was used in patients with a normal baseline coagulation parameters. Initially the dialyser and tubings were rinsed with 5000 IU of unfractionated heparin dissolved in 1000 mL of isotonic saline. Unfractionated heparin was then given pre-filter at the rate of 250-500 IU/hr so as to achieve a target aPTT of 45-55 secs. (Heparin group). aPTT measurements were done every 6 th hourly or earlier if patient developed significant prolongation of aPTT. Patients with a baseline aPTT of > 55 secs, platelet count of < 40,000/mm 3 , prior history of heparin allergy or heparin induced thrombocytopenia, intracranial hemorrhage within three months, gastrointestinal hemorrhage requiring a transfusion of greater than two units of blood within three months, active bleeding within three days or significant trauma within three days and evidence of irreversible coagulopathy as a result of liver failure, disseminated intravascular coagulation or a coagulation factor deficiency did not receive any heparin  and dialyser and tubing was flushed with 100-150 mL of isotonic saline at 30 mins interval (Heparin free group). Circuits were changed if any clots appeared in the circuit.
Primary outcome was to compare the average filter life in both the groups. Coagulation of filter (Filter failure) was defined as visible clotforming at the inlet and outlet of filter or in the lines with a more than 50% decrease in ultrafiltration rate. Filter life was noted in hours. 
Secondary outcome included analysis of bleeding episodes and transfusion requirements in both the groups. The definition of hemorrhage was derived from Levine et al.  Hemorrhage was considered major if bleeding occurred intracranially, retroperitoneally or resulted in death or in the replacement of two or more units of blood within 24 hrs. All other hemorrhagic episodes were considered to be "minor". During the study, transfusion threshold guideline utilized was Hb of 7.0 g/dL. 
| Statistical Analysis|| |
Analysis was done using SPSS software version 7.0 for Windows. Students T test was used for discrete variable while Chi square test was used for categorical variables. P < 0.05 was considered to be statistically significant.
| Results|| |
Of a total of 425 patients with ARF admitted in the ICU 65 (15%) received CRRT, 35 in heparin group and 30 in heparin free group. Baseline demographic data is shown in [Table 1]. Laboratory investigations revealed a significantly low platelet count and a prolonged aPTT in the heparin free group as compared to the heparin group, [Table 2].
There was no statistical difference in CRRT parameters in both groups, [Table 3].
The mean filter life was comparable in both the groups in the range of 24-26 hrs. Total number of bleeding episodes were significantly higher in the heparin group (16 vs 4: P< 0.05) as also bleeding episodes per patient which was also significantly higher in heparin group (0.45 vs 0.13: P< 0.05). Majority of the bleeding episodes were trivial in both the groups. However one patient who received heparin had a severe intacranial hemorrhage. Average blood transfusion requirement was two in the heparin group and one in the heparin free group but the difference was not statistically significant, [Table 4].
Mortality was 71% in the heparin group and 67% in the heparin free group P> 0.05, [Table 5].
| Discussion|| |
Effective anticoagulation of the extracorporeal circuit is important in managing patients with CRRT for optimal filter performance especially in patients with multiorgan failure (MOF). Systemic heparin is associated with bleeding complications and hence cannot be given in patients with coagulopathy. In developing countries like India where heparin is the only anticoagulant used during CRRT, the only alternative is use of isotonic saline flushes to maintain the extracorporeal circuit.
In our study, only 15% of ARF patients received CRRT compared to more than 25% in developed countries. ,, The most important limiting factor in the under utility of CRRT is the cost of the therapy. There is no proper insurance system in India and with a significant number of the patient population (about 70-80%) being lower middle class and poor, CRRT therapy is out of the reach of these patients.
Although our heparin free group included more patients of diabetes mellitus and sepsis, and were more older (63.25 ± 15.24 years), the saline flushes were still able to maintain filter life comparable to the heparin group. Hemodynamically mediated ARF (HMARF) was significantly more common in the later group.
A higher incidence of coagulopathy reflected by significantly lower mean platelet count and a significantly prolonged aPTT was present in the heparin free group as also noted by Uchino et al  .
Mean filter life was also similar in both the groups which is similar to other studies. ,,, However, Palsson et al reported a decreased filter life and filter performance in the heparin free group.  In contrast, only one study by Tan et al reported a significantly longer circuit life in heparin free group (43% of filters managed with saline flushes lasted for more than 30 hrs). 
Number of bleeding episodes and the bleeding episodes per patient was significantly higher in the heparin group. Majority of the bleeding episodes were trivial but one major bleeding episode was noted in the heparin group. Reeves et al  in his analysis of 22 patients receiving unfractionated heparin noted seven bleeding episode of which three were trivial and 4 were major episodes Palsson R et al  noted one major bleeding episode in 17 filters receiving heparin with no bleeding episode in the no anticoagulation group using 15 filters. Average blood transfusion requirement, though higher in the heparin group, was not statistically significant.
Overall mortality in our study was 70% similar to other studies. ,,, The high mortality in patients receiving CRRT probably reflects the fact that only severely ill patients or those who worsen with other therapies are taken up for CRRT. There was no difference in mortality in both the groups indicating that with or without anticoagulation, these patients at higher risk of bleeding receive an adequate dose of CRRT with good filter performance.
In summary, CRRT with isotonic saline flushes is an effective mode of maintaining patency of the circuit especially in patients with high risk bleeding profile. It is associated with an acceptable filter life, lesser risk of bleeding and fewer blood transfusion requirements compared to heparin anticoagulation.
| References|| |
|1.||Uchino S, Kellum JA, Bellomo R, et al. Acute renal failure in critically ill patients: A Multinational, Multicentre study. JAMA 2005;295(7): 813-8. |
|2.||Block CA, Manning HL. Prevention of acute renal failure in critically ill. Am J Respir Crit Care Med 2002;165:320-4. [PUBMED] [FULLTEXT] |
|3.||Clermont G, Acker CG, Angus DC, et al. Renal failure in the ICU: Comparison of the impact of acute renal failure and end stage renal disease on ICU outcomes. Kidney Int 2002;62:986-96. [PUBMED] [FULLTEXT] |
|4.||Siegel N, Shah S. Acute renal failure: Directions for the next decade. J Am Soc Nephrol 2003;14:2176-7. |
|5.||Martin GS, Mannino DM, Eaton S, Moss M. The epidemiology of sepsis in the United States from 1979 through 2000. N Engl J Med 2003; 348:1546-54. [PUBMED] [FULLTEXT] |
|6.||Liano F, Pascual J. Outcomes in acute renal failure. Semin Nephrol 1998;18:541-50. |
|7.||McCarthy JT. Prognosis of patients with acute renal failure in the intensive-care unit: A tale of two eras. Mayo Clin Proc 1996;71:117-26. [PUBMED] |
|8.||Brivet FG, Kleinknecht DJ, Loirat P, Landais PJ. Acute renal failure in intensive care unitsCauses, outcome, and prognostic factors of hospital mortality: A prospective, multicenter study. French Study Group on Acute Renal Failure. Crit Care Med 1996;24:192-8. [PUBMED] [FULLTEXT] |
|9.||Liano F, Pascual J. Epidemiology of acute renal failure: A prospective, multicenter, communitybased study. Madrid Acute Renal Failure Study Group. Kidney Int 1996;50:811-8. |
|10.||Manns M, Sigler MH, Teehan BP. Continuous renal replacement therapies: An update. Am J Kidney Dis 1998;32:185-207. [PUBMED] [FULLTEXT] |
|11.||Kellum JA, Mehta RL, Angus DC, et al. The first international consensus conference on continuous renal replacement therapy. Kidney Int 2002;62:1855-63. [PUBMED] [FULLTEXT] |
|12.||Mehta RL, Letteri JM. Current status of renal replacement therapy for acute renal failure. A survey of US nephrologists. The National Kidney Foundation Council on Dialysis. Am J Nephrol 1999;19:377-82. |
|13.||Kramer P, Wigger W, Rieger J, Matthaei D, Scheler F. Arteriovenous haemofiltration: A new and simple method for treatment of overhydrated patients resistant to diuretics. Klin Wochenschr 1977;55:1121-2. [PUBMED] |
|14.||Webb AR, Mythen MG, Jacobson D, et al. Maintaining blood flow in the extracorporeal circuit: Hemostasis and anticoagulation. Int Care Med 1995;21:84-93. |
|15.||Abramson S, Niles JL. Anticoagulation in continuous renal replacement therapy. Curr Opin Nephrol Hypertens 1999;8(6):701-7. |
|16.||Kutsogiannis DJ, Gibney RT, Stollery D, Gao J. Regional citrate versus systemic heparin anticoagulation for continuous renal replacement in critically ill patients. Kidney Int 2006;67: 2361-7. |
|17.||van de Wetering J, Westendorp RG, van der Hoeven JG, Stolk B, Feuth JD, Chang PC. Heparin use in continuous renal replacement procedures: The struggle between filter coagulation and patient haemorrhage. J Am Soc Nephrol 1996;7:145-50. [PUBMED] [FULLTEXT] |
|18.||Levine MN, Hirsh J, Kelton JG. Heparin induced bleeding. In: Lane DA, Lindahl U, Eds. Heparin: Chemical and biological propertiesClinical applications. London: Edward Arnold; 1989:517-31. |
|19.||Hebert PC, Wells G, Blajchman MA, et al. A Multicentre, randomized, controlled clinical trial of transfusion requirements in critical care. Transfusion Requirements in Critical Care Investigators, Canadian Critical Care Trials Group. N Engl J Med 1999;340:409-17. |
|20.||Uchino S, Fealy N, Baldwin I, Morimatsu H, Bellomo R. Continuous venovenous hemofiltration without anticoagulation. ASAIO J 2004;50(1):76-80. |
|21.||Morabito S, Guzzo I, Solazzo A, Muzi L, Luciani R, Pierucci A. Continuous renal replacement therapies: Anticoagulation in the critically ill at high risk of bleeding. J Nephrol 2003;16(4):566-71. |
|22.||Bellomo R, Teede H, Boyce N. Anticoagulant regimens in acute continuous hemodiafiltration: A comparative study. Intensive Care Med 1993;19(6):329-32. |
|23.||Martin PY, Chevrolet JC, Suter P, Favre H. Anticoagulation in patients treated by continuous venovenous hemofiltration: A retrospecttive study. Am J Kidney Dis 1994;24(5): 806-12. |
|24.||Palsson R, Laliberte KA, Niles JL. Choice of replacement solution and anticoagulant in continuous venovenous hemofiltration. Clin Nephrol 2006;65(1):34-42. |
|25.||Tan HK, Baldwin I, Bellomo R. Continuous venovenous hemofiltration without anticoagulation in high-risk patients. Intensive Care Med 2000;26(11):1652-7. |
|26.||Reeves JH, Cumming AR, Gallagher L, O'Brien JL, Santamaria JD. A controlled trial of lowmolecular-weight heparin (dalteparin) versus unfractionated heparin as anticoagulant during continuous venovenous hemodialysis with filtration. Crit Care Med 1999;27(10):2224-8. |
|27.||Lobo V, Joshi A, Joseph S, et al. Continuous venovenous hemofiltration for ARF in critically ill patients. Indian J Crit Care Med 2004; 8:148-52. |
|28.||Chuasuwan A, Gojaseni P, Chittinandana A. Continuous venovenous hemofiltration in Bhumibol Adulyadej Hospital. J Med Assoc Thai 2006;89(Suppl 2):S86-7. [PUBMED] |
|29.||Guerin C, Girard R, Sellit JM, Ayzac L. Intermittent versus continuous renal replacement therapy for acute renal failure in intensive care units: Results from a multicenter prospective epidemiological survey. Intensive Care Med 2002;28:1411-8. |
|30.||Mehta RL, Pascual MT, Soroko S, et al. Spectrum of acute renal failure in the intensive care unit: The PICARD experience. Kidney Int 2004;66:1613-21. [PUBMED] [FULLTEXT] |
Department of Nephrology, Mediciti Hospitals 5-9-22, Secretariat Road, Hyderabad, Andhra Pradesh, 500063
[Table 1], [Table 2], [Table 3], [Table 5], [Table 4]
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