The Real Cost of Conventional Hemodialysis in Critically III Patients* Rinaldo Bellomo, MD, PhD Department of Intensive Care Australian and New Zealand Intensive Care Research Centre Melbourne, Australia Antoine G. Schneider, MD Department of Intensive Care Centre Hospitalo-Universitaire Vaudois Lausanne, Switzerland
T
he choice of modality for renal replacement therapy (RRT) in critically ill patients has been a matter of controversy for over 20 years (1-5). Two dominant choices are available: conventional intermittent hemodialysis (IHD) and continuous renal replacement therapy (CRRT). The protagonists of CRRT have long argued that this modality is associated with greater hemodynamic stability; full and continuous control of volume status; steady control of electrolyte and acid-base status; temperature control; avoidance of solute swings and cerebral edema; and superior uremic control (6). To this, the protagonists of conventional IHD have responded that IHD avoids continuous anticoagulation and its associated risks; it can be easily deployed at the bedside; if delivered with due attention, it can be hemodynamically safe; it has stood the test of time; it allows the patient to achieve greater mobility; and it is significantly cheaper (7). This controversy is fuelled by the lack of sufficiently powered, high-quality randomized controlled trials (RCTs). It is also supported by the perception that most patients transition from one modality to another and that the available evidence (however limited in quality, magnitude and scope) shows no difference in mortality. As evidenced by the two largest phase III RCTs of RRT dose in ICU (8, 9), this uncertainty has spawned at least two styles of practice. One is characterized by the use of CRRT in vasopressor-dependent patients and of IHD in vasopressor-independent patients with movement in and out of each modality according to their clinical condition (8). The other is characterized by the exclusive use of CRRT in ICU (9).
'See also p. 868. Key Words: continuous hemofiltration; continuous renal replacement therapy; end-stage kidney failure; hemodialysis; renal recovery Dr. Bellomo consulted for, lectured for, and received support for travel from Gambro, Baxter, and BBraun. His institution received grant support from Baxter. Dr. Schneider has disclosed that he does not have any potential conflicts of interest. Copyright © 2013 by the Society of Critical Care Medicine and uppincott Williams & Wilkins DOI: 10.1097/CCM.0000000000000076
990
www.ccmjournal.org
One appears dominant in the United States, and the other is dominant in Australia and New Zealand. Elsewhere, there is great variability based on local culture, resources, and expertise. These two approaches have come under scrutiny once again after the publication of the above RCTs, because despite similar patient characteristics and illness severity at randomization (10), the "conventional IHD with CRRT for hemodynamic instability" model of care was associated with much greater renal nonrecovery at 28 days than the "exclusive CRRT" model (25.8% vs 8.0%). Thus, an old question was brought back to life: does conventional IHD delay or prevent renal recovery after acute kidney injury (AKI) in critically ill patients? It is this important question that the article by Wald et al (11), in this issue of Critical Care Medicine, addresses with an outstanding observational study. Taking advantage of the linked administrative health databases of the province of Ontario, Wald et al (11) identified more than 13,000 patients who received RRT in the ICU and classified them on the intention-to-treat principle (the first modality of RRT prescribed). Then, they matched 2,004 CRRT patients (87% of the total) with 2,004 IHD patients. The matching was extraordinary in its comprehensiveness and used dozens of variables from "neighborhood income" to "diabetes" and from "carotid Doppler ultrasonography in the previous 5 years" to "chronic kidney disease" to develop a robust propensity score, which the authors combined with acute characteristics, such as the presence of sepsis and mechanical ventilation. After such extensive matching, they attempted to establish whether, in patients who survived to 90 days of initiation of therapy, chronic dialysis occurred with different frequency in those first treated with IHD compared with those first treated with CRRT. They found that at 90 days after initiation of IHD, 20.8% of patients were on dialysis compared with 16.4% of CRRT patients {p < 0.0003). At follow-up, after a mean of approximately 3 years, the prevalence of chronic dialysis was 6.5 per 100 person years among patients initially treated with CRRT compared with 8.2 among patients initially treated with IHD (p < 0.0001; hazard ratio 0.75). This difference held in different subgroups and was particularly strong in patients with chronic kidney disease, the very patients often preferentially selected for IHD. The investigators then comprehensively assessed their findings with multiple sensitivity analyses (any CRRT vs exclusive IHD; follow-up commencing at time of first RRT; patients who were alive and dialysis independent at 90 days). Their findings were broadly confirmed in these groups although CIs for the hazard ratios changed according to group and sample size. These findings follow a meta-analysis published this year involving all studies since 2000 (n = 50), which also focused on renal recovery (12). In a combined April 2014' Volume 42 • Number 4
Editorials
cohort of 1,716 IHD-treated patients and 2,255 CRRT-treated patients, the findings were the same: starting treatment with IHD was associated with a significant decrease in renal recovery among survivors. The economic case for using conventional IHD collapses as the real cost of IHD is revealed by the study by Wald et al (11). Assuming that 50% of patients with severe AKI are alive at 90 days (8, 9), for every 100 patient treated with conventional IHD, 2.7 extra patients will be on chronic dialysis for a median period of more than 3 years. Assuming a total cost of care for 1 year of dialysis in the United States of between $129,000 and $173,000 (13), this effect on recovery adds approximately $150,000 per year for 3 years to the cost of patient care ($4,500 per IHD-treated patient). Given the limited estimated extra cost of CRRT ( 14, 15 ), the financial case for conventional IHD is turned upside down. These considerations do not even touch upon the morbidity price and the social, psychological, and biological costs of chronic dialysis. Should clinicians wait for a definitive RCT before responding to these findings? Such a trial would have to randomize more than 2,600 patients to have a 90% power of detecting the same difference reported by Wald et al (11) at an a of 0.05. The largest trial conducted so far in this field by those who continue to use conventional IHD in ICU patients required more than 3.5 years to recruit 1,200 patients. A renal recovery trial (if ever conducted) would therefore likely require at least 10 years from design to completion. In the meanwhile, in the United States alone, perhaps more than 30,000 patients with AKI per year continue to be exposed to the nonrecovery risks associated with IHD. In this context, business as usual cannot be logically justified. The time for clinicians to make choices is now.
REFERENCES 1. Uchino S, Kellum JA, Bellomo R, et al; Beginning and Ending Supportive Therapy for the Kidney (BEST Kidney) Investigators; Acute renal failure in critically ill patients; A multinational, multicenter study. JAMA 2005; 294:813-818
Critical Care Medicine
2. Kierdorf H: Continuous versus intermittent treatment: Clinical results in acute renal failure. Contrib Nephrol 1991 ; 93;1 -12 3. Pannu N, Klarenbach S, Wiebe N, et al; Alberta Kidney Disease Network; Renal replacement therapy in patients with acute renal failure: A systematic review. JAMA 2008; 299:793-805 4. Mehta RL, MoDonald B, Gabbai FB, et al; Collaborative Group for Treatment of ARF in the ICU: A randomized clinical trial of continuous versus intermittent dialysis for acute renal failure. Kidney Int 2001 ; 60:1154-1163 5. Vinsonneau C, Camus C, Combes A, et al; Hemodiafe Study Group: Continuous venovenous haemodiafiltration versus intermittent haemodialysis for acute renal failure in patients with multiple-organ dysfunction syndrome: A multicentre randomised trial. Lancet 2006; 368:379-385 6. Bellomo R, Ronco C: Acute renal failure in the intensive care unit: Adequacy of dialysis and the case for continuous therapies. Nephrol Dial Transplant 1996; 11:424-428 7. Vanholder R, Van Biesen W, Hoste E, et al: Pro/con debate: Continuous versus intermittent dialysis for acute kidney injury: A never-ending story yet approaching the finish? Crit Care 2011 ; 15;204 8. Palevsky PM, Zhang JH, C'Connor TZ, et al; VA/NIH Acute Renal Failure Trial Network: Intensity of renal support in critically ill patients with acute kidney injury. N EngI J Med 2008; 359;7-20 9. Bellomo R, Cass A, Cole L, et al; RENAL Replacement Therapy Study Investigators: Intensity of continuous renal-replacement therapy in critically ill patients. N EngI J Med 2009; 361 ;1627-1638 10. Schneider AG, Lipcsey M, Bailey M, et al: Relationship between illness severity scores in acute kidney injury. Crit Care Resusc 201 2; 14:53-55 11. Wald R, Shariff SZ, Adhikari NKJ, et al: The Association Between Renal Replacement Therapy Modality and Long-Term Cutcomes Among Critically III Adults With Acute Kidney Injury; A Retrospective Cohort Study. Crit Care Med 2014; 42:868-877 12. Schneider AG, Bellomo R, Bagshaw SM, et al: Choice of renal replacement therapy modality and dialysis dependenoe after acute kidney injury: A systematic review and meta-analysis. Intensive Care Med 2013; 39:987-997 13. Berger A, Edelsberg J, Inglese GW, et al: Cost comparison of peritoneal dialysis versus hemodialysis in end-stage renal disease. Am J Manag Care 2009; 15;509-518 14. Srisawat N, Lawsin L, Uchino S, et al; BEST Kidney Investigators: Cost of acute renai replacement therapy in the intensive care unit: Results from The Beginning and Ending Supportive Therapy for the Kidney (BEST Kidney) study. Crit Care 2010; 14:R46 15. Manns B, Doig CJ, Lee H, et al: Cost of acute renal failure requiring dialysis in the intensive care unit; Clinical and resource implications of renal recovery. Crit Care Med 2003; 31:449-455
www.ccmjournal.org
991
Copyright of Critical Care Medicine is the property of Lippincott Williams & Wilkins and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
T
he choice of modality for renal replacement therapy (RRT) in critically ill patients has been a matter of controversy for over 20 years (1-5). Two dominant choices are available: conventional intermittent hemodialysis (IHD) and continuous renal replacement therapy (CRRT). The protagonists of CRRT have long argued that this modality is associated with greater hemodynamic stability; full and continuous control of volume status; steady control of electrolyte and acid-base status; temperature control; avoidance of solute swings and cerebral edema; and superior uremic control (6). To this, the protagonists of conventional IHD have responded that IHD avoids continuous anticoagulation and its associated risks; it can be easily deployed at the bedside; if delivered with due attention, it can be hemodynamically safe; it has stood the test of time; it allows the patient to achieve greater mobility; and it is significantly cheaper (7). This controversy is fuelled by the lack of sufficiently powered, high-quality randomized controlled trials (RCTs). It is also supported by the perception that most patients transition from one modality to another and that the available evidence (however limited in quality, magnitude and scope) shows no difference in mortality. As evidenced by the two largest phase III RCTs of RRT dose in ICU (8, 9), this uncertainty has spawned at least two styles of practice. One is characterized by the use of CRRT in vasopressor-dependent patients and of IHD in vasopressor-independent patients with movement in and out of each modality according to their clinical condition (8). The other is characterized by the exclusive use of CRRT in ICU (9).
'See also p. 868. Key Words: continuous hemofiltration; continuous renal replacement therapy; end-stage kidney failure; hemodialysis; renal recovery Dr. Bellomo consulted for, lectured for, and received support for travel from Gambro, Baxter, and BBraun. His institution received grant support from Baxter. Dr. Schneider has disclosed that he does not have any potential conflicts of interest. Copyright © 2013 by the Society of Critical Care Medicine and uppincott Williams & Wilkins DOI: 10.1097/CCM.0000000000000076
990
www.ccmjournal.org
One appears dominant in the United States, and the other is dominant in Australia and New Zealand. Elsewhere, there is great variability based on local culture, resources, and expertise. These two approaches have come under scrutiny once again after the publication of the above RCTs, because despite similar patient characteristics and illness severity at randomization (10), the "conventional IHD with CRRT for hemodynamic instability" model of care was associated with much greater renal nonrecovery at 28 days than the "exclusive CRRT" model (25.8% vs 8.0%). Thus, an old question was brought back to life: does conventional IHD delay or prevent renal recovery after acute kidney injury (AKI) in critically ill patients? It is this important question that the article by Wald et al (11), in this issue of Critical Care Medicine, addresses with an outstanding observational study. Taking advantage of the linked administrative health databases of the province of Ontario, Wald et al (11) identified more than 13,000 patients who received RRT in the ICU and classified them on the intention-to-treat principle (the first modality of RRT prescribed). Then, they matched 2,004 CRRT patients (87% of the total) with 2,004 IHD patients. The matching was extraordinary in its comprehensiveness and used dozens of variables from "neighborhood income" to "diabetes" and from "carotid Doppler ultrasonography in the previous 5 years" to "chronic kidney disease" to develop a robust propensity score, which the authors combined with acute characteristics, such as the presence of sepsis and mechanical ventilation. After such extensive matching, they attempted to establish whether, in patients who survived to 90 days of initiation of therapy, chronic dialysis occurred with different frequency in those first treated with IHD compared with those first treated with CRRT. They found that at 90 days after initiation of IHD, 20.8% of patients were on dialysis compared with 16.4% of CRRT patients {p < 0.0003). At follow-up, after a mean of approximately 3 years, the prevalence of chronic dialysis was 6.5 per 100 person years among patients initially treated with CRRT compared with 8.2 among patients initially treated with IHD (p < 0.0001; hazard ratio 0.75). This difference held in different subgroups and was particularly strong in patients with chronic kidney disease, the very patients often preferentially selected for IHD. The investigators then comprehensively assessed their findings with multiple sensitivity analyses (any CRRT vs exclusive IHD; follow-up commencing at time of first RRT; patients who were alive and dialysis independent at 90 days). Their findings were broadly confirmed in these groups although CIs for the hazard ratios changed according to group and sample size. These findings follow a meta-analysis published this year involving all studies since 2000 (n = 50), which also focused on renal recovery (12). In a combined April 2014' Volume 42 • Number 4
Editorials
cohort of 1,716 IHD-treated patients and 2,255 CRRT-treated patients, the findings were the same: starting treatment with IHD was associated with a significant decrease in renal recovery among survivors. The economic case for using conventional IHD collapses as the real cost of IHD is revealed by the study by Wald et al (11). Assuming that 50% of patients with severe AKI are alive at 90 days (8, 9), for every 100 patient treated with conventional IHD, 2.7 extra patients will be on chronic dialysis for a median period of more than 3 years. Assuming a total cost of care for 1 year of dialysis in the United States of between $129,000 and $173,000 (13), this effect on recovery adds approximately $150,000 per year for 3 years to the cost of patient care ($4,500 per IHD-treated patient). Given the limited estimated extra cost of CRRT ( 14, 15 ), the financial case for conventional IHD is turned upside down. These considerations do not even touch upon the morbidity price and the social, psychological, and biological costs of chronic dialysis. Should clinicians wait for a definitive RCT before responding to these findings? Such a trial would have to randomize more than 2,600 patients to have a 90% power of detecting the same difference reported by Wald et al (11) at an a of 0.05. The largest trial conducted so far in this field by those who continue to use conventional IHD in ICU patients required more than 3.5 years to recruit 1,200 patients. A renal recovery trial (if ever conducted) would therefore likely require at least 10 years from design to completion. In the meanwhile, in the United States alone, perhaps more than 30,000 patients with AKI per year continue to be exposed to the nonrecovery risks associated with IHD. In this context, business as usual cannot be logically justified. The time for clinicians to make choices is now.
REFERENCES 1. Uchino S, Kellum JA, Bellomo R, et al; Beginning and Ending Supportive Therapy for the Kidney (BEST Kidney) Investigators; Acute renal failure in critically ill patients; A multinational, multicenter study. JAMA 2005; 294:813-818
Critical Care Medicine
2. Kierdorf H: Continuous versus intermittent treatment: Clinical results in acute renal failure. Contrib Nephrol 1991 ; 93;1 -12 3. Pannu N, Klarenbach S, Wiebe N, et al; Alberta Kidney Disease Network; Renal replacement therapy in patients with acute renal failure: A systematic review. JAMA 2008; 299:793-805 4. Mehta RL, MoDonald B, Gabbai FB, et al; Collaborative Group for Treatment of ARF in the ICU: A randomized clinical trial of continuous versus intermittent dialysis for acute renal failure. Kidney Int 2001 ; 60:1154-1163 5. Vinsonneau C, Camus C, Combes A, et al; Hemodiafe Study Group: Continuous venovenous haemodiafiltration versus intermittent haemodialysis for acute renal failure in patients with multiple-organ dysfunction syndrome: A multicentre randomised trial. Lancet 2006; 368:379-385 6. Bellomo R, Ronco C: Acute renal failure in the intensive care unit: Adequacy of dialysis and the case for continuous therapies. Nephrol Dial Transplant 1996; 11:424-428 7. Vanholder R, Van Biesen W, Hoste E, et al: Pro/con debate: Continuous versus intermittent dialysis for acute kidney injury: A never-ending story yet approaching the finish? Crit Care 2011 ; 15;204 8. Palevsky PM, Zhang JH, C'Connor TZ, et al; VA/NIH Acute Renal Failure Trial Network: Intensity of renal support in critically ill patients with acute kidney injury. N EngI J Med 2008; 359;7-20 9. Bellomo R, Cass A, Cole L, et al; RENAL Replacement Therapy Study Investigators: Intensity of continuous renal-replacement therapy in critically ill patients. N EngI J Med 2009; 361 ;1627-1638 10. Schneider AG, Lipcsey M, Bailey M, et al: Relationship between illness severity scores in acute kidney injury. Crit Care Resusc 201 2; 14:53-55 11. Wald R, Shariff SZ, Adhikari NKJ, et al: The Association Between Renal Replacement Therapy Modality and Long-Term Cutcomes Among Critically III Adults With Acute Kidney Injury; A Retrospective Cohort Study. Crit Care Med 2014; 42:868-877 12. Schneider AG, Bellomo R, Bagshaw SM, et al: Choice of renal replacement therapy modality and dialysis dependenoe after acute kidney injury: A systematic review and meta-analysis. Intensive Care Med 2013; 39:987-997 13. Berger A, Edelsberg J, Inglese GW, et al: Cost comparison of peritoneal dialysis versus hemodialysis in end-stage renal disease. Am J Manag Care 2009; 15;509-518 14. Srisawat N, Lawsin L, Uchino S, et al; BEST Kidney Investigators: Cost of acute renai replacement therapy in the intensive care unit: Results from The Beginning and Ending Supportive Therapy for the Kidney (BEST Kidney) study. Crit Care 2010; 14:R46 15. Manns B, Doig CJ, Lee H, et al: Cost of acute renal failure requiring dialysis in the intensive care unit; Clinical and resource implications of renal recovery. Crit Care Med 2003; 31:449-455
www.ccmjournal.org
991
Copyright of Critical Care Medicine is the property of Lippincott Williams & Wilkins and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
