Acute Kidney Injury After Cardiac Surgery: The Injury That Keeps on Hurting?* John R. Prowle, MA, M B BChir, MSc, M D, MRCP, FFICM C hristopher J. K irw an, M D , M R C P, F F IC M
Adult Critical Care Unit The Royal London Hospital Barts Health NHS Trust London, United Kingdom lthough the association between acute kidney injury (AKI) and adverse outcomes during acute hospitaliza tion is well known, the strong correlation between AKI and the development or progression of chronic kidney disease (CKD) (1) has been less appreciated. Risk and severity of CKD after AKI appears incrementally related to AKI severity (2), whereas development of CKD is associated with long-term risk of death (3). In particular, AKI is strongly associated with long-term cardiovascular morbidity and mortality (4,5). Con sequently, the development persistent renal dysfunction after AKI and its associated outcomes is now recognized as being of key importance (6). In this issue of Critical Care Medicine, Engoren et al (7) examine the influence of renal dysfunction on short- and long-term survival in a retrospective analysis of 1,543 adults undergoing cardiac surgery over a 4-year period. They found that severity of AKI was associated with both short-term (< 30 days) and long-term risk of death (median follow-up, 3.5 years), an association that persisted after allowing for poten tial confounders in multivariable analysis. This connection between postoperative AKI and increased risk of death after discharge underscores the significant long-term impact of AKI beyond the acute episode in the cardiac surgical population. Determining the mechanisms by which AKI is associated with adverse chronic outcomes is critical, as this may allow us to better plan follow-up and examine preventative interven tions. However, the occurrence of AKI is likely to be a sensitive indicator of poor physiological reserve and severity of general perioperative insult, as well as being a direct causative influ ence on early and late mortality. Thus, determining the modi fiable, causative influence of AKI or CKD on risk of death is complex. In this, the results of this study are helpful, as when hospital discharge creatinine at was included as a baseline
A
*See also p. 2069. Key Words: acute kidney injury; cardiac surgery; outcomes Dr. Prowle consulted for Gambro AB, is employed by Barts Health NHS Trust, and lectured for Gambro AB and Alere. His institution received grant support from Bart and the London Charity. Dr. Kirwan has disclosed that he does not have any potential conflicts of interest. Copyright © 2014 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins
DOI: 10.1097/CCM.0000000000000453 2142
w w w .c c m jo u r n a l.o r g
hazard in multivariable survival analysis both AKI severity and baseline creatinine became nonsignificant predictors for death after discharge, implying the degree of persistent renal dysfunction at discharge was most important renal predictor of long-term survival. This finding supports a hypothesis that the main influence of AKI on longer term survival is as a risk factor for development of CKD. The association between renal dysfunction and mortality seen in this study was substantial; in the survival model presented, a lm g/dL higher discharge creatinine was predicted to almost double the rate of death over time in compared to an otherwise identical population of patients with a lower discharge creatinine. The study has some limitations; it was restricted to cardiac surgical patients (who have specific risk factors for AKI) and was conducted in a single center, so the results may not be widely generalizable. However, the conclusions are strength ened by the availability of actual baseline creatinines in a largely elective surgical population. The findings are also in line with other reports associating degree of CKD after AKI with long term risk of death (2). However, although follow-up data on survival were obtained, no information is provided on rates of renal recovery, CKD development, and CKD progression after discharge, which could have strengthened these findings. Finally, information on cause of death is unavailable; given the association between AKI, CKD, and cardiovascular risk, one might expect this population of cardiac surgery patients to be a particular risk of adverse cardiovascular events if they developed AKI and/or CKD, a possibility that would warrant specific investigation in future studies. There are some other interesting features of this study that should be highlighted. The authors defined a category of “min imal AKI” as any increase in creatinine from baseline, not suf ficient to meet creatinine criteria for AKI (> 0.3mg/dL rise in 48 hours). Occurrence of minimal AKI did significantly influ ence risk of death after discharge in a multivariable survival model, a finding in accord with a previous report (8). However, it is more interesting to consider the 45% of all patients that were in the “no AKI group,” where creatinine did not rise at all. In group, the “highest creatinine” in the 14 days after surgery was the same or lower than the baseline value, something that would be unusual by chance variation alone. This suggests that a normal response to surgery in most patients is for creatinine to fall and, therefore, that a maintained serum creatinine after surgery may in fact reflect significant AKI. This inference cor responds with conclusions from a recent study of patients after community cardiac arrest (9). In that study, marked decrease in creatinine occurred in most patients; however, in patients where creatinine remained similar to baseline, a kinetic analy sis (accounting for illness-associated decrease in creatinine generation) suggested a substantial fall in glomerular filtration September 2014 • Volume 42 • Number 9
Editorials
had actually occurred, a conclusion supported by significantly higher mortality and increased urinary neutrophil gelatinaseassociated lipocalin in those patients. Seen it this light, it is not surprising that “minimal AKI” could be associated with later development of CKD and sustained risk of adverse outcomes. Importantly, in the survival model developed by Engoren et al (7), discharge creatinine was continuously related to risk of death, so although patients with higher creatinine were at highest predicted risk, patients with unchanged creatinine would have higher predicted mortality than the many patients whose creatinine was below baseline at discharge. So what can we conclude from this report and the current evidence regarding outcomes after AKI? First, that persistent renal dysfunction after cardiac surgery has an important influ ence on long-term outcomes and the mechanisms of this asso ciation require further exploration. If, as seems likely, CKD is a major causative factor for morbidity and mortality after AKI, then clinical pathways for follow-up of AKI survivors are essential to allow early diagnosis of CKD and permit interven tions minimize its impact. Furthermore, studies of AKI should strongly emphasize development of CKD as a crucial, patientcentered outcome. However, as Engoren et al (7) state in their introduction: “While AKI is a well-established prognostic risk factor, the science of evaluating renal functional recovery is much less mature” and assessing the true prevalence and impli cations of renal dysfunction after cardiac surgery complicated by AKI may require better tools than serum creatinine.
R E FE R E N C E S 1. Coca SG, Singanamala S, Parikh CR: Chronic kidney disease after acute kidney injury: A systematic review and meta-analysis. Kidney Int 2 0 1 2 ;8 1 :4 4 2 -4 4 8 2. Chawla LS, Amdur RL, Amodeo S, et al: The severity of acute kid ney injury predicts progression to chronic kidney disease. Kidney Int 2011; 7 9 :1 3 6 1 -1 3 6 9 3. Lai CF, Wu VC, Huang TM, et al; the National Taiwan University Hospital Study Group on Acute Renal Failure (NSARF): Kidney func tion decline after a non-dialysis-requiring acute kidney injury is associ ated with higher long-term mortality in critically ill survivors. Crit Care 2012; 16:R 123 4. Wu VC, Wu CH, Huang TM, et al; NSARF Group: Long-term risk of coronary events after AKI. J Am Soc Nephrol 2014; 2 5 :5 9 5 -6 0 5 5. Chawla LS, Amdur RL, Shaw AD, et al: Association between AKI and long-term renal and cardiovascular outcomes in United States veter ans. Clin J Am Soc Nephrol 2014; 9 :4 4 8 -4 5 6 6. Leung KC, Tonelli M, James MT: Chronic kidney disease follow ing acute kidney injury-risk and outcomes. Nat Rev Nephrol 2013; 9 :7 7 -8 5 7. Engoren M, Habib RH, Arslanian-Engoren C, et al: The Effect of Acute Kidney Injury and Discharge Creatinine Level on Mortality Following Cardiac Surgery. Crit Care Med 2014; 4 2 :2 0 6 9 -2 0 7 4 8. Lassnigg A, Schmidlin D, Mouhieddine M, et al: Minimal changes of serum creatinine predict prognosis in patients after cardiothoracic surgery: A prospective cohort study. J Am Soc Nephrol 2004; 1 5 :1 5 9 7 -1 6 0 5 9. Pickering JW, Ralib AM, Endre ZH: Combining creatinine and volume kinetics identifies missed cases of acute kidney injury following car diac arrest. Crit Care 2013; 17:R7
“The Rhythm Is Gonna Get You...”: Extracorporeal Membrane Oxygenation With and Without Intra-Aortic Balloon Pumps* Herbert Patrick, MD, MSEE Division of Critical Care ARIA Health Philadelphia, PA
xtracorporeal life support (ECLS) includes devices for extracorporeal membrane oxygenation (ECMO) (1), carbon dioxide removal (2), and cardiopulmonary
E
*See also p. 2075. Key Words: cardiogenic shock; extracorporeal life support; extracorporeal membrane oxygenation; intra-aortic balloon pump Dr. Patrick received support for participation in review activities from, and lectured for, Hutchinson Technology. His institution received grant support from Hutchinson Technology. Copyright © 2014 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins
DOI: 10.1097/CCM.0000000000000452
Critical Care Medicine
resuscitation (3). ECLS differs from classic cardiopulmonary bypass, as invented by Gibbon (4), by using catheter access in the internal jugular vein, with the catheter placed using local anesthesia, versus transthoracic catheters placed using general anesthesia and the ability to maintain longer duration of sup port for days versus hours. ECMO saves lives of both critically ill infants and adults. Data compiled by The Extracorporeal Life Support Organiza tion, an international consortium of healthcare professionals and scientists, show that in 2013, ECMO therapy was used to treat 4,357 patients at 223 centers worldwide (5). The types of ECMO differ by the vascular access connections. Venous to arterial ECMO (VA-ECMO) supports the cardiovascular sys tem only but not the lungs, and so it is used to treat patients such as those with refractory cardiogenic shock. Venous to venous ECMO (W -ECMO) supports the lungs only but not the cardiovascular system, and so it is used to treat patients such as those with refractory hypoxia. VA- versus W -ECM O w w w .c c m jo u r n a l.o r g
2 1 43
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.
Adult Critical Care Unit The Royal London Hospital Barts Health NHS Trust London, United Kingdom lthough the association between acute kidney injury (AKI) and adverse outcomes during acute hospitaliza tion is well known, the strong correlation between AKI and the development or progression of chronic kidney disease (CKD) (1) has been less appreciated. Risk and severity of CKD after AKI appears incrementally related to AKI severity (2), whereas development of CKD is associated with long-term risk of death (3). In particular, AKI is strongly associated with long-term cardiovascular morbidity and mortality (4,5). Con sequently, the development persistent renal dysfunction after AKI and its associated outcomes is now recognized as being of key importance (6). In this issue of Critical Care Medicine, Engoren et al (7) examine the influence of renal dysfunction on short- and long-term survival in a retrospective analysis of 1,543 adults undergoing cardiac surgery over a 4-year period. They found that severity of AKI was associated with both short-term (< 30 days) and long-term risk of death (median follow-up, 3.5 years), an association that persisted after allowing for poten tial confounders in multivariable analysis. This connection between postoperative AKI and increased risk of death after discharge underscores the significant long-term impact of AKI beyond the acute episode in the cardiac surgical population. Determining the mechanisms by which AKI is associated with adverse chronic outcomes is critical, as this may allow us to better plan follow-up and examine preventative interven tions. However, the occurrence of AKI is likely to be a sensitive indicator of poor physiological reserve and severity of general perioperative insult, as well as being a direct causative influ ence on early and late mortality. Thus, determining the modi fiable, causative influence of AKI or CKD on risk of death is complex. In this, the results of this study are helpful, as when hospital discharge creatinine at was included as a baseline
A
*See also p. 2069. Key Words: acute kidney injury; cardiac surgery; outcomes Dr. Prowle consulted for Gambro AB, is employed by Barts Health NHS Trust, and lectured for Gambro AB and Alere. His institution received grant support from Bart and the London Charity. Dr. Kirwan has disclosed that he does not have any potential conflicts of interest. Copyright © 2014 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins
DOI: 10.1097/CCM.0000000000000453 2142
w w w .c c m jo u r n a l.o r g
hazard in multivariable survival analysis both AKI severity and baseline creatinine became nonsignificant predictors for death after discharge, implying the degree of persistent renal dysfunction at discharge was most important renal predictor of long-term survival. This finding supports a hypothesis that the main influence of AKI on longer term survival is as a risk factor for development of CKD. The association between renal dysfunction and mortality seen in this study was substantial; in the survival model presented, a lm g/dL higher discharge creatinine was predicted to almost double the rate of death over time in compared to an otherwise identical population of patients with a lower discharge creatinine. The study has some limitations; it was restricted to cardiac surgical patients (who have specific risk factors for AKI) and was conducted in a single center, so the results may not be widely generalizable. However, the conclusions are strength ened by the availability of actual baseline creatinines in a largely elective surgical population. The findings are also in line with other reports associating degree of CKD after AKI with long term risk of death (2). However, although follow-up data on survival were obtained, no information is provided on rates of renal recovery, CKD development, and CKD progression after discharge, which could have strengthened these findings. Finally, information on cause of death is unavailable; given the association between AKI, CKD, and cardiovascular risk, one might expect this population of cardiac surgery patients to be a particular risk of adverse cardiovascular events if they developed AKI and/or CKD, a possibility that would warrant specific investigation in future studies. There are some other interesting features of this study that should be highlighted. The authors defined a category of “min imal AKI” as any increase in creatinine from baseline, not suf ficient to meet creatinine criteria for AKI (> 0.3mg/dL rise in 48 hours). Occurrence of minimal AKI did significantly influ ence risk of death after discharge in a multivariable survival model, a finding in accord with a previous report (8). However, it is more interesting to consider the 45% of all patients that were in the “no AKI group,” where creatinine did not rise at all. In group, the “highest creatinine” in the 14 days after surgery was the same or lower than the baseline value, something that would be unusual by chance variation alone. This suggests that a normal response to surgery in most patients is for creatinine to fall and, therefore, that a maintained serum creatinine after surgery may in fact reflect significant AKI. This inference cor responds with conclusions from a recent study of patients after community cardiac arrest (9). In that study, marked decrease in creatinine occurred in most patients; however, in patients where creatinine remained similar to baseline, a kinetic analy sis (accounting for illness-associated decrease in creatinine generation) suggested a substantial fall in glomerular filtration September 2014 • Volume 42 • Number 9
Editorials
had actually occurred, a conclusion supported by significantly higher mortality and increased urinary neutrophil gelatinaseassociated lipocalin in those patients. Seen it this light, it is not surprising that “minimal AKI” could be associated with later development of CKD and sustained risk of adverse outcomes. Importantly, in the survival model developed by Engoren et al (7), discharge creatinine was continuously related to risk of death, so although patients with higher creatinine were at highest predicted risk, patients with unchanged creatinine would have higher predicted mortality than the many patients whose creatinine was below baseline at discharge. So what can we conclude from this report and the current evidence regarding outcomes after AKI? First, that persistent renal dysfunction after cardiac surgery has an important influ ence on long-term outcomes and the mechanisms of this asso ciation require further exploration. If, as seems likely, CKD is a major causative factor for morbidity and mortality after AKI, then clinical pathways for follow-up of AKI survivors are essential to allow early diagnosis of CKD and permit interven tions minimize its impact. Furthermore, studies of AKI should strongly emphasize development of CKD as a crucial, patientcentered outcome. However, as Engoren et al (7) state in their introduction: “While AKI is a well-established prognostic risk factor, the science of evaluating renal functional recovery is much less mature” and assessing the true prevalence and impli cations of renal dysfunction after cardiac surgery complicated by AKI may require better tools than serum creatinine.
R E FE R E N C E S 1. Coca SG, Singanamala S, Parikh CR: Chronic kidney disease after acute kidney injury: A systematic review and meta-analysis. Kidney Int 2 0 1 2 ;8 1 :4 4 2 -4 4 8 2. Chawla LS, Amdur RL, Amodeo S, et al: The severity of acute kid ney injury predicts progression to chronic kidney disease. Kidney Int 2011; 7 9 :1 3 6 1 -1 3 6 9 3. Lai CF, Wu VC, Huang TM, et al; the National Taiwan University Hospital Study Group on Acute Renal Failure (NSARF): Kidney func tion decline after a non-dialysis-requiring acute kidney injury is associ ated with higher long-term mortality in critically ill survivors. Crit Care 2012; 16:R 123 4. Wu VC, Wu CH, Huang TM, et al; NSARF Group: Long-term risk of coronary events after AKI. J Am Soc Nephrol 2014; 2 5 :5 9 5 -6 0 5 5. Chawla LS, Amdur RL, Shaw AD, et al: Association between AKI and long-term renal and cardiovascular outcomes in United States veter ans. Clin J Am Soc Nephrol 2014; 9 :4 4 8 -4 5 6 6. Leung KC, Tonelli M, James MT: Chronic kidney disease follow ing acute kidney injury-risk and outcomes. Nat Rev Nephrol 2013; 9 :7 7 -8 5 7. Engoren M, Habib RH, Arslanian-Engoren C, et al: The Effect of Acute Kidney Injury and Discharge Creatinine Level on Mortality Following Cardiac Surgery. Crit Care Med 2014; 4 2 :2 0 6 9 -2 0 7 4 8. Lassnigg A, Schmidlin D, Mouhieddine M, et al: Minimal changes of serum creatinine predict prognosis in patients after cardiothoracic surgery: A prospective cohort study. J Am Soc Nephrol 2004; 1 5 :1 5 9 7 -1 6 0 5 9. Pickering JW, Ralib AM, Endre ZH: Combining creatinine and volume kinetics identifies missed cases of acute kidney injury following car diac arrest. Crit Care 2013; 17:R7
“The Rhythm Is Gonna Get You...”: Extracorporeal Membrane Oxygenation With and Without Intra-Aortic Balloon Pumps* Herbert Patrick, MD, MSEE Division of Critical Care ARIA Health Philadelphia, PA
xtracorporeal life support (ECLS) includes devices for extracorporeal membrane oxygenation (ECMO) (1), carbon dioxide removal (2), and cardiopulmonary
E
*See also p. 2075. Key Words: cardiogenic shock; extracorporeal life support; extracorporeal membrane oxygenation; intra-aortic balloon pump Dr. Patrick received support for participation in review activities from, and lectured for, Hutchinson Technology. His institution received grant support from Hutchinson Technology. Copyright © 2014 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins
DOI: 10.1097/CCM.0000000000000452
Critical Care Medicine
resuscitation (3). ECLS differs from classic cardiopulmonary bypass, as invented by Gibbon (4), by using catheter access in the internal jugular vein, with the catheter placed using local anesthesia, versus transthoracic catheters placed using general anesthesia and the ability to maintain longer duration of sup port for days versus hours. ECMO saves lives of both critically ill infants and adults. Data compiled by The Extracorporeal Life Support Organiza tion, an international consortium of healthcare professionals and scientists, show that in 2013, ECMO therapy was used to treat 4,357 patients at 223 centers worldwide (5). The types of ECMO differ by the vascular access connections. Venous to arterial ECMO (VA-ECMO) supports the cardiovascular sys tem only but not the lungs, and so it is used to treat patients such as those with refractory cardiogenic shock. Venous to venous ECMO (W -ECMO) supports the lungs only but not the cardiovascular system, and so it is used to treat patients such as those with refractory hypoxia. VA- versus W -ECM O w w w .c c m jo u r n a l.o r g
2 1 43
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.
