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Therapeutic Apheresis and Dialysis 2015; 19(1):8–15 doi: 10.1111/1744-9987.12196 © 2014 The Authors Therapeutic Apheresis and Dialysis © 2014 International Society for Apheresis
Regional Citrate Anticoagulation for Continuous Renal Replacement Therapy in the Perioperative Care of Liver Transplant Recipients: A Single Center Experience Christoph Sponholz,1 Utz Settmacher,2 Michael Bauer,1,3 and Andreas Kortgen1,3 1
Department of Anaesthesiology and Critical Care Medicine, 2Department of General, Visceral and Vascular Surgery and 3Center for Sepsis Control and Care (CSCC), Integrated Research and Treatment Center, Jena University Hospital , Jena, Germany
Abstract: Kidney injury with concomitant hemodialysis is a common finding in perioperative care of liver transplant patients. The aim of this study was to evaluate disturbances in acid-base status, electrolyte balance and citrate accumulation during hemodialysis with regional citrate anticoagulation in perioperative care of liver transplant recipients. A retrospective, single center evaluation was conducted of patients with severe liver dysfunction receiving renal replacement therapy in the perioperative care of liver transplantation in a multidisciplinary ICU of a university hospital. Within 5 days of ICU stay, 89 patients undergoing liver transplantation received regional citrate anticoagulation for hemodialysis. During the study period pH (7.39 [7.33/7.43] vs. 7.44 [7.39/7.47], P-value = 0.014), base excess values (−0.9 [−5.08/2.35] vs. 4.3 [1.93/8.21], P-value = 0.001) and standard bicarbonate (23.6 [20/26.9] vs. 28.2 [26.2/32.2], P-value = 0.001) significantly increased,
whereas lactate levels (2.6 [1.60/4.45] vs. 1.25 [0.98/1.9], P-value = 0.071) and Catot/Caion-ratio decreased or remained below the upper reference. Hypocalcemia appeared mostly within 48 h after dialysis initiation. Although sodium levels increased during the observation, rates of hypernatremia were comparable between hemodialysis days 1 and 5. Hemodialysis using regional citrate anticoagulation remains a challenge in the perioperative care of liver transplant recipients. Major attention must be paid to acid-base disturbances and citrate accumulation within 48 h after dialysis initiation. Nevertheless, regional citrate anticoagulation in liver dysfunction is a feasible and valuable tool, when limitations and pitfalls are adequately considered. Key Words: Acid-base status, Citrate anticoagulation, Electrolyte balance, Hemodialysis, Intensive care, Liver failure.
End-stage liver disease and consecutive liver transplantation often lead to renal dysfunction requiring hemodialysis (1). Due to massive coagulopathy or perioperative bleeding complications, anticoagulation during hemodialysis provides a challenge in the intensive care setting of liver failure patients. In recent years regional citrate anticoagulation (RCA) for renal replacement therapy has become more and more popular, not only among critically ill patients (2). Hence, RCA has resulted in longer filter life spans and reduced bleeding risks compared to heparin-based anticoagulation protocols and few studies indicate reduced mortality in critically ill patients (3).
However, the role of RCA in patients with severe liver dysfunction has been less evaluated, although RCA could provide advantages especially in this patient cohort. Currently, only a few prospectively designed and controlled clinical studies also report safety and efficacy of RCA for hemodialysis among critically ill patients with liver dysfunction (4,5). However, several limitations and pitfalls emerged in this special patient cohort leading to careful monitoring of clinical conditions and laboratory markers. In this respect, especially disturbances in acid-base status and electrolyte imbalances may complicate the patients’ course with various deleterious consequences. Moreover, citrate accumulation due to liver dysfunction may result in bleeding complications itself and is an independent risk factor for patient survival (6). Recognizing these complications and pitfalls may therefore not only improve performance of RCA, but also increase patient safety.
Received December 2013; revised February 2014. Address correspondence and reprint requests to Dr Andreas Kortgen, Department of Anaesthesiology and Critical Care Medicine, Jena University Hospital, Erlanger Allee 101, D—07747 Jena, Germany. Email: [email protected]
8
Dialysis in Liver Failure Patients Aim of this study was to report the experience in RCA among patients with severe liver dysfunction in the early perioperative care of liver transplant recipients in a multidisciplinary intensive care unit of a university hospital. Particular focus was placed on disturbances in acid-base status, electrolyte balance and citrate accumulation during the first week of continuous veno-venous hemodialysis (CVVHD). PATIENTS AND METHODS Study design The study was a retrospective, single-center evaluation of patients with severe liver dysfunction receiving renal replacement therapy (RRT) in the perioperative care of liver transplantation in a multidisciplinary intensive care unit (ICU) of a university hospital. The study was approved by the local ethics committee, which waived informed consent because of the anonymous and observational nature of the study. Patient recruitment The patient data management system (COPRA, V.5.24.338, COPRA System GmbH, Sasbachwalden, Germany) was scanned for patients undergoing liver transplantation (LTx) between January 2007 and December 2011. Within this period, 284 single organ liver transplantations were performed. Re-liver transplantations within 7 days were not evaluated separately. Characteristics of hemodialysis According to our standard protocol RRT was performed in CVVHD mode (Multifiltrate, Fresenius Medical Care, Bad Homburg, Germany). Median blood flow rates were adjusted depending on patients’ hemodynamic conditions. Dialysate flow rate was adjusted to a dialysis dose of 25–35 mL/kg bodyweight/h (Ci-Ca Dialysate K2, Fresenius Medical Care; containing: 133 mmol/L Na+, 2.0 mmol/L K+, 0 mmol/L Ca++, 0.75 mmol/L Mg++, 118.5 mmol/L Cl−, 20 mmol/L HCO3− and 1.0 g/L glucose). Standard anticoagulation was maintained with regional citrate anticoagulation (4% Sodium Citrate, Fresenius Kabi, Bad Homburg, Germany), adjusted to a postfilter ionized calcium level between 0.25–0.35 mmol/L. To restore postfilter calcium homeostasis, CaCl2 (1N Calcium-Chloride solution, Serumwerk Bernburg AG; Bernburg, Germany) was replaced, predefined by the dialysate flow rate. Vascular access for RRT was implemented via a triple lumen dialysis catheters (TRILYSE Expert, Vygon, © 2014 The Authors Therapeutic Apheresis and Dialysis © 2014 International Society for Apheresis
9
Aachen, Germany) either in the jugular, subclavian or femoral vein. Maximum duration of CVVHD was 72 h per dialysis set. Statistical analysis Data are presented as median values (25th/75th percentile) and categorical data as number and percentage, unless otherwise indicated. Categorical variables were analyzed by χ2 test. Dependent parameters on dialysis day 1 and 5 were analyzed by the Wilcoxon test. Resulting P-values were adjusted for multiple comparisons using the Bonferroni method. Correlation between impaired liver dysfunction (represented either by model for end stage liver disease (MELD) scores or plasma disappearance rate of indocyanine green (PDRICG)) and citrate accumulation (defined by total-to-ionized calcium ratio) were calculated using the Spearman-Rho test. A P-value 37), patients had lower ionized calcium levels compared to the lower MELD groups, but these differences returned to normal values during progression of citrate dialysis (12). Of note, Kalb et al. could not find any citrate accumulation within a group of critically ill patients in a mixed surgical patient cohort
Ther Apher Dial, Vol. 19, No. 1, 2015
under citrate anticoagulation for CVVHD (9), probably with very low numbers of patients with liver dysfunction. Finally, Meier-Kriesche found a violation of the Catot/Caion-ratio in 33% of patients with liver failure, while none of the patients without liver dysfunction experienced citrate accumulation under citrate anticoagulation. Interestingly, patients with a violation of the Catot/Caion-ratio >2.5 had a higher mortality compared to patients with normal Catot/ Caion-ratio, either with or without liver dysfunction. The authors therefore propose an early correction of calcium and citrate infusion rates to adopt a normal Catot/Caion-ratio (13). This finding was also supported by the study of Link et al., who found higher mortality rates in critically ill patients with an increased Catot/Caion-ratio >2.5 under citrate anticoagulation. In patients with liver failure and/or multi-organ dysfunction syndrome, the authors found an association to increased Catot/Caion-ratio (6). Taking these findings together, citrate accumulation under RCA can occur in patients suffering from liver dysfunction and might have an impact on patients survival. Nevertheless, particularly in the early phase of dialysis, violations in calcium homeostasis may occur and patients should therefore be monitored closely. Another challenge in perioperative care of liver transplant recipients is maintaining a stable electrolyte balance. Moreover, additional dialysis may enhance sodium imbalance caused by sodium-citrate solutions for anticoagulation. Within our patient cohort, sodium levels increased during the study period, but stayed within the normal range of 136–145 mmol/L. The chance to violate the upper reference was equal on dialysis day 1 and 5. Hypernatremia may thus not be enhanced by sodium-citrate anticoagulation. A recent metaanalysis focusing on the efficacy and safety of RCA in critically ill patients reported on negligible amounts of hypernatremia occurring during hemodialysis. Interestingly, rates of hypernatremia were comparable between RCA and other coagulation protocols (14). Although, hypernatremia may not be enhanced by RCA, sodium imbalances were associated with patient outcome in surgical intensive care patients even if sodium values stayed within the normal range (15) and especially in cirrhotic patients (16). Thus, sodium should be controlled and monitored carefully during citrate anticoagulation for CVVHD. As expected, potassium levels decreased or remained low under hemodialysis and were of minor concern. As we and others could show (5,9,17), CVVHD using RCA was able to reduce kidney function parameters, that is, creatinine and urea, during the course of hemodialysis. CVVHD with RCA may © 2014 The Authors Therapeutic Apheresis and Dialysis © 2014 International Society for Apheresis
Dialysis in Liver Failure Patients therefore achieve the goals for RRT, namely control of electrolytes, acid-base status and effective removal of urea and creatinine as surrogate parameters for efficacy. Limitations of our analysis can be found in the retrospective design and the relatively small patient cohort. Nevertheless, our study represents a realistic view on the daily care of liver transplant recipients requiring hemodialysis and may therefore not be biased by focused prospective examinations with special care in these patients. CONCLUSION Hemodialysis using regional citrate anticoagulation remains a challenge in the perioperative care of liver transplant recipients. Major attention must be paid especially to acid-base disturbances and citrate accumulation. The majority of these imbalances, whether due to the anticoagulation regimen or the underlying disease course, is restricted to the early phase (∼48 h) after initiation of dialysis. Nevertheless, regional citrate anticoagulation in liver dysfunction is a feasible and valuable tool, when limitations and pitfalls are adequately considered. Modified dialysis protocols, adjusted citrate or dialysis solutions (as proposed by Saner et al. (5) or Morgera et al. (17)) for this specific patient cohort could possibly further improve feasibility and safety of regional citrate anticoagulation in patients with liver failure. REFERENCES 1. Weber ML, Ibrahim HN, Lake JR. Renal dysfunction in liver transplant recipients: evaluation of the critical issues. Liver Transpl 2012;18:1290–301. 2. Hetzel GR, Schmitz M, Wissing H et al. Regional citrate versus systemic heparin for anticoagulation in critically ill patients on continuous venovenous haemofiltration: a prospective randomized multicentre trial. Nephrol Dial Transplant 2011;26:232–9.
© 2014 The Authors Therapeutic Apheresis and Dialysis © 2014 International Society for Apheresis
15
3. Oudemans-van Straaten HM, Kellum JA, Bellomo R. Clinical review: anticoagulation for continuous renal replacement therapy—heparin or citrate? Crit Care 2011;15:202. 4. Schultheiss C, Saugel B, Phillip V et al. Continuous venovenous hemodialysis with regional citrate anticoagulation in patients with liver failure: a prospective observational study. Crit Care 2012;16:R162. 5. Saner FH, Treckmann JW, Geis A et al. Efficacy and safety of regional citrate anticoagulation in liver transplant patients requiring post-operative renal replacement therapy. Nephrol Dial Transplant 2012;27:1651–7. 6. Link A, Klingele M, Speer T et al. Total-to-ionized calcium ratio predicts mortality in continuous renal replacement therapy with citrate anticoagulation in critically ill patients. Crit Care 2012;16:R97. 7. Tolwani AJ, Wille KM. Anticoagulation for continuous renal replacement therapy. Semin Dial 2009;22:141–5. 8. Morgera S, Scholle C, Voss G et al. Metabolic complications during regional citrate anticoagulation in continuous venovenous hemodialysis: single-center experience. Nephron Clin Pract 2004;97:c131–136. 9. Kalb R, Kram R, Morgera S, Slowinski T, Kindgen-Milles D. Regional citrate anticoagulation for high volume continuous venovenous hemodialysis in surgical patients with high bleeding risk. Ther Apher Dial 2013;17:202–12. 10. Finkel KW, Podoll AS. Complications of continuous renal replacement therapy. Semin Dial 2009;22:155–9. 11. Bakker AJ, Boerma EC, Keidel H, Kingma P, van der Voort PH. Detection of citrate overdose in critically ill patients on citrate-anticoagulated venovenous haemofiltration: use of ionised and total/ionised calcium. Clin Chem Lab Med 2006;44:962–6. 12. Balogun RA, Turgut F, Caldwell S, Abdel-Rahman EM. Regional citrate anticoagulation in critically ill patients with liver and kidney failure. J Nephrol 2012;25:113–9. 13. Meier-Kriesche HU, Gitomer J, Finkel K, DuBose T. Increased total to ionized calcium ratio during continuous venovenous hemodialysis with regional citrate anticoagulation. Crit Care Med 2001;29:748–52. 14. Zhang Z, Hongying N. Efficacy and safety of regional citrate anticoagulation in critically ill patients undergoing continuous renal replacement therapy. Intensive Care Med 2012;38:20– 8. 15. Sakr Y, Rother S, Ferreira AM et al. Fluctuations in serum sodium level are associated with an increased risk of death in surgical ICU patients. Crit Care Med 2013;41:133– 42. 16. Bengus A, Babiuc RD. Hyponatremia—predictor of adverse prognosis in cirrhosis. J Med Life 2012;5:176–8. 17. Morgera S, Schneider M, Slowinski T et al. A safe citrate anticoagulation protocol with variable treatment efficacy and excellent control of the acid-base status. Crit Care Med 2009;37:2018–24.
Ther Apher Dial, Vol. 19, No. 1, 2015
Therapeutic Apheresis and Dialysis 2015; 19(1):8–15 doi: 10.1111/1744-9987.12196 © 2014 The Authors Therapeutic Apheresis and Dialysis © 2014 International Society for Apheresis
Regional Citrate Anticoagulation for Continuous Renal Replacement Therapy in the Perioperative Care of Liver Transplant Recipients: A Single Center Experience Christoph Sponholz,1 Utz Settmacher,2 Michael Bauer,1,3 and Andreas Kortgen1,3 1
Department of Anaesthesiology and Critical Care Medicine, 2Department of General, Visceral and Vascular Surgery and 3Center for Sepsis Control and Care (CSCC), Integrated Research and Treatment Center, Jena University Hospital , Jena, Germany
Abstract: Kidney injury with concomitant hemodialysis is a common finding in perioperative care of liver transplant patients. The aim of this study was to evaluate disturbances in acid-base status, electrolyte balance and citrate accumulation during hemodialysis with regional citrate anticoagulation in perioperative care of liver transplant recipients. A retrospective, single center evaluation was conducted of patients with severe liver dysfunction receiving renal replacement therapy in the perioperative care of liver transplantation in a multidisciplinary ICU of a university hospital. Within 5 days of ICU stay, 89 patients undergoing liver transplantation received regional citrate anticoagulation for hemodialysis. During the study period pH (7.39 [7.33/7.43] vs. 7.44 [7.39/7.47], P-value = 0.014), base excess values (−0.9 [−5.08/2.35] vs. 4.3 [1.93/8.21], P-value = 0.001) and standard bicarbonate (23.6 [20/26.9] vs. 28.2 [26.2/32.2], P-value = 0.001) significantly increased,
whereas lactate levels (2.6 [1.60/4.45] vs. 1.25 [0.98/1.9], P-value = 0.071) and Catot/Caion-ratio decreased or remained below the upper reference. Hypocalcemia appeared mostly within 48 h after dialysis initiation. Although sodium levels increased during the observation, rates of hypernatremia were comparable between hemodialysis days 1 and 5. Hemodialysis using regional citrate anticoagulation remains a challenge in the perioperative care of liver transplant recipients. Major attention must be paid to acid-base disturbances and citrate accumulation within 48 h after dialysis initiation. Nevertheless, regional citrate anticoagulation in liver dysfunction is a feasible and valuable tool, when limitations and pitfalls are adequately considered. Key Words: Acid-base status, Citrate anticoagulation, Electrolyte balance, Hemodialysis, Intensive care, Liver failure.
End-stage liver disease and consecutive liver transplantation often lead to renal dysfunction requiring hemodialysis (1). Due to massive coagulopathy or perioperative bleeding complications, anticoagulation during hemodialysis provides a challenge in the intensive care setting of liver failure patients. In recent years regional citrate anticoagulation (RCA) for renal replacement therapy has become more and more popular, not only among critically ill patients (2). Hence, RCA has resulted in longer filter life spans and reduced bleeding risks compared to heparin-based anticoagulation protocols and few studies indicate reduced mortality in critically ill patients (3).
However, the role of RCA in patients with severe liver dysfunction has been less evaluated, although RCA could provide advantages especially in this patient cohort. Currently, only a few prospectively designed and controlled clinical studies also report safety and efficacy of RCA for hemodialysis among critically ill patients with liver dysfunction (4,5). However, several limitations and pitfalls emerged in this special patient cohort leading to careful monitoring of clinical conditions and laboratory markers. In this respect, especially disturbances in acid-base status and electrolyte imbalances may complicate the patients’ course with various deleterious consequences. Moreover, citrate accumulation due to liver dysfunction may result in bleeding complications itself and is an independent risk factor for patient survival (6). Recognizing these complications and pitfalls may therefore not only improve performance of RCA, but also increase patient safety.
Received December 2013; revised February 2014. Address correspondence and reprint requests to Dr Andreas Kortgen, Department of Anaesthesiology and Critical Care Medicine, Jena University Hospital, Erlanger Allee 101, D—07747 Jena, Germany. Email: [email protected]
8
Dialysis in Liver Failure Patients Aim of this study was to report the experience in RCA among patients with severe liver dysfunction in the early perioperative care of liver transplant recipients in a multidisciplinary intensive care unit of a university hospital. Particular focus was placed on disturbances in acid-base status, electrolyte balance and citrate accumulation during the first week of continuous veno-venous hemodialysis (CVVHD). PATIENTS AND METHODS Study design The study was a retrospective, single-center evaluation of patients with severe liver dysfunction receiving renal replacement therapy (RRT) in the perioperative care of liver transplantation in a multidisciplinary intensive care unit (ICU) of a university hospital. The study was approved by the local ethics committee, which waived informed consent because of the anonymous and observational nature of the study. Patient recruitment The patient data management system (COPRA, V.5.24.338, COPRA System GmbH, Sasbachwalden, Germany) was scanned for patients undergoing liver transplantation (LTx) between January 2007 and December 2011. Within this period, 284 single organ liver transplantations were performed. Re-liver transplantations within 7 days were not evaluated separately. Characteristics of hemodialysis According to our standard protocol RRT was performed in CVVHD mode (Multifiltrate, Fresenius Medical Care, Bad Homburg, Germany). Median blood flow rates were adjusted depending on patients’ hemodynamic conditions. Dialysate flow rate was adjusted to a dialysis dose of 25–35 mL/kg bodyweight/h (Ci-Ca Dialysate K2, Fresenius Medical Care; containing: 133 mmol/L Na+, 2.0 mmol/L K+, 0 mmol/L Ca++, 0.75 mmol/L Mg++, 118.5 mmol/L Cl−, 20 mmol/L HCO3− and 1.0 g/L glucose). Standard anticoagulation was maintained with regional citrate anticoagulation (4% Sodium Citrate, Fresenius Kabi, Bad Homburg, Germany), adjusted to a postfilter ionized calcium level between 0.25–0.35 mmol/L. To restore postfilter calcium homeostasis, CaCl2 (1N Calcium-Chloride solution, Serumwerk Bernburg AG; Bernburg, Germany) was replaced, predefined by the dialysate flow rate. Vascular access for RRT was implemented via a triple lumen dialysis catheters (TRILYSE Expert, Vygon, © 2014 The Authors Therapeutic Apheresis and Dialysis © 2014 International Society for Apheresis
9
Aachen, Germany) either in the jugular, subclavian or femoral vein. Maximum duration of CVVHD was 72 h per dialysis set. Statistical analysis Data are presented as median values (25th/75th percentile) and categorical data as number and percentage, unless otherwise indicated. Categorical variables were analyzed by χ2 test. Dependent parameters on dialysis day 1 and 5 were analyzed by the Wilcoxon test. Resulting P-values were adjusted for multiple comparisons using the Bonferroni method. Correlation between impaired liver dysfunction (represented either by model for end stage liver disease (MELD) scores or plasma disappearance rate of indocyanine green (PDRICG)) and citrate accumulation (defined by total-to-ionized calcium ratio) were calculated using the Spearman-Rho test. A P-value 37), patients had lower ionized calcium levels compared to the lower MELD groups, but these differences returned to normal values during progression of citrate dialysis (12). Of note, Kalb et al. could not find any citrate accumulation within a group of critically ill patients in a mixed surgical patient cohort
Ther Apher Dial, Vol. 19, No. 1, 2015
under citrate anticoagulation for CVVHD (9), probably with very low numbers of patients with liver dysfunction. Finally, Meier-Kriesche found a violation of the Catot/Caion-ratio in 33% of patients with liver failure, while none of the patients without liver dysfunction experienced citrate accumulation under citrate anticoagulation. Interestingly, patients with a violation of the Catot/Caion-ratio >2.5 had a higher mortality compared to patients with normal Catot/ Caion-ratio, either with or without liver dysfunction. The authors therefore propose an early correction of calcium and citrate infusion rates to adopt a normal Catot/Caion-ratio (13). This finding was also supported by the study of Link et al., who found higher mortality rates in critically ill patients with an increased Catot/Caion-ratio >2.5 under citrate anticoagulation. In patients with liver failure and/or multi-organ dysfunction syndrome, the authors found an association to increased Catot/Caion-ratio (6). Taking these findings together, citrate accumulation under RCA can occur in patients suffering from liver dysfunction and might have an impact on patients survival. Nevertheless, particularly in the early phase of dialysis, violations in calcium homeostasis may occur and patients should therefore be monitored closely. Another challenge in perioperative care of liver transplant recipients is maintaining a stable electrolyte balance. Moreover, additional dialysis may enhance sodium imbalance caused by sodium-citrate solutions for anticoagulation. Within our patient cohort, sodium levels increased during the study period, but stayed within the normal range of 136–145 mmol/L. The chance to violate the upper reference was equal on dialysis day 1 and 5. Hypernatremia may thus not be enhanced by sodium-citrate anticoagulation. A recent metaanalysis focusing on the efficacy and safety of RCA in critically ill patients reported on negligible amounts of hypernatremia occurring during hemodialysis. Interestingly, rates of hypernatremia were comparable between RCA and other coagulation protocols (14). Although, hypernatremia may not be enhanced by RCA, sodium imbalances were associated with patient outcome in surgical intensive care patients even if sodium values stayed within the normal range (15) and especially in cirrhotic patients (16). Thus, sodium should be controlled and monitored carefully during citrate anticoagulation for CVVHD. As expected, potassium levels decreased or remained low under hemodialysis and were of minor concern. As we and others could show (5,9,17), CVVHD using RCA was able to reduce kidney function parameters, that is, creatinine and urea, during the course of hemodialysis. CVVHD with RCA may © 2014 The Authors Therapeutic Apheresis and Dialysis © 2014 International Society for Apheresis
Dialysis in Liver Failure Patients therefore achieve the goals for RRT, namely control of electrolytes, acid-base status and effective removal of urea and creatinine as surrogate parameters for efficacy. Limitations of our analysis can be found in the retrospective design and the relatively small patient cohort. Nevertheless, our study represents a realistic view on the daily care of liver transplant recipients requiring hemodialysis and may therefore not be biased by focused prospective examinations with special care in these patients. CONCLUSION Hemodialysis using regional citrate anticoagulation remains a challenge in the perioperative care of liver transplant recipients. Major attention must be paid especially to acid-base disturbances and citrate accumulation. The majority of these imbalances, whether due to the anticoagulation regimen or the underlying disease course, is restricted to the early phase (∼48 h) after initiation of dialysis. Nevertheless, regional citrate anticoagulation in liver dysfunction is a feasible and valuable tool, when limitations and pitfalls are adequately considered. Modified dialysis protocols, adjusted citrate or dialysis solutions (as proposed by Saner et al. (5) or Morgera et al. (17)) for this specific patient cohort could possibly further improve feasibility and safety of regional citrate anticoagulation in patients with liver failure. REFERENCES 1. Weber ML, Ibrahim HN, Lake JR. Renal dysfunction in liver transplant recipients: evaluation of the critical issues. Liver Transpl 2012;18:1290–301. 2. Hetzel GR, Schmitz M, Wissing H et al. Regional citrate versus systemic heparin for anticoagulation in critically ill patients on continuous venovenous haemofiltration: a prospective randomized multicentre trial. Nephrol Dial Transplant 2011;26:232–9.
© 2014 The Authors Therapeutic Apheresis and Dialysis © 2014 International Society for Apheresis
15
3. Oudemans-van Straaten HM, Kellum JA, Bellomo R. Clinical review: anticoagulation for continuous renal replacement therapy—heparin or citrate? Crit Care 2011;15:202. 4. Schultheiss C, Saugel B, Phillip V et al. Continuous venovenous hemodialysis with regional citrate anticoagulation in patients with liver failure: a prospective observational study. Crit Care 2012;16:R162. 5. Saner FH, Treckmann JW, Geis A et al. Efficacy and safety of regional citrate anticoagulation in liver transplant patients requiring post-operative renal replacement therapy. Nephrol Dial Transplant 2012;27:1651–7. 6. Link A, Klingele M, Speer T et al. Total-to-ionized calcium ratio predicts mortality in continuous renal replacement therapy with citrate anticoagulation in critically ill patients. Crit Care 2012;16:R97. 7. Tolwani AJ, Wille KM. Anticoagulation for continuous renal replacement therapy. Semin Dial 2009;22:141–5. 8. Morgera S, Scholle C, Voss G et al. Metabolic complications during regional citrate anticoagulation in continuous venovenous hemodialysis: single-center experience. Nephron Clin Pract 2004;97:c131–136. 9. Kalb R, Kram R, Morgera S, Slowinski T, Kindgen-Milles D. Regional citrate anticoagulation for high volume continuous venovenous hemodialysis in surgical patients with high bleeding risk. Ther Apher Dial 2013;17:202–12. 10. Finkel KW, Podoll AS. Complications of continuous renal replacement therapy. Semin Dial 2009;22:155–9. 11. Bakker AJ, Boerma EC, Keidel H, Kingma P, van der Voort PH. Detection of citrate overdose in critically ill patients on citrate-anticoagulated venovenous haemofiltration: use of ionised and total/ionised calcium. Clin Chem Lab Med 2006;44:962–6. 12. Balogun RA, Turgut F, Caldwell S, Abdel-Rahman EM. Regional citrate anticoagulation in critically ill patients with liver and kidney failure. J Nephrol 2012;25:113–9. 13. Meier-Kriesche HU, Gitomer J, Finkel K, DuBose T. Increased total to ionized calcium ratio during continuous venovenous hemodialysis with regional citrate anticoagulation. Crit Care Med 2001;29:748–52. 14. Zhang Z, Hongying N. Efficacy and safety of regional citrate anticoagulation in critically ill patients undergoing continuous renal replacement therapy. Intensive Care Med 2012;38:20– 8. 15. Sakr Y, Rother S, Ferreira AM et al. Fluctuations in serum sodium level are associated with an increased risk of death in surgical ICU patients. Crit Care Med 2013;41:133– 42. 16. Bengus A, Babiuc RD. Hyponatremia—predictor of adverse prognosis in cirrhosis. J Med Life 2012;5:176–8. 17. Morgera S, Schneider M, Slowinski T et al. A safe citrate anticoagulation protocol with variable treatment efficacy and excellent control of the acid-base status. Crit Care Med 2009;37:2018–24.
Ther Apher Dial, Vol. 19, No. 1, 2015
