ADULT CARDIAC
Complications of Extracorporeal Membrane Oxygenation for Treatment of Cardiogenic Shock and Cardiac Arrest: A Meta-Analysis of 1,866 Adult Patients Richard Cheng, MD, Rory Hachamovitch, MD, Michelle Kittleson, MD, PhD, Jignesh Patel, MD, PhD, Francisco Arabia, MD, Jaime Moriguchi, MD, Fardad Esmailian, MD, and Babak Azarbal, MD Cedars-Sinai Heart Institute, Los Angeles, California, and Department of Cardiovascular Medicine, Heart and Vascular Institute, Cleveland Clinic, Cleveland, Ohio
Background. Venoarterial extracorporeal membrane oxygenation (ECMO) has been used successfully for treatment of cardiogenic shock or cardiac arrest. The exact complication rate is not well understood, in part because of small study sizes. In the absence of large clinical trials, performance of pooled analysis represents the best method for ascertaining complication rates for ECMO. Methods. A systematic PubMed search was conducted on ECMO for treatment of cardiogenic shock or cardiac arrest in adult patients only, updated to November 2012. Studies with more than 10 patients published in the year 2000 or later that reported complication rates for ECMO were included. Specific complications analyzed included lower extremity ischemia, fasciotomy or compartment syndrome, amputation, stroke, neurologic complications, acute kidney injury, renal replacement therapy, major or significant bleeding, rethoracotomy for bleeding or tamponade, and significant infection. For studies that included overlapping patients, the largest study was included and the others excluded. Cochran’s Q and I-squared were calculated. A more conservative randomeffects model was chosen for all analyses. Results. Twenty studies were included in the analyses encompassing 1,866 patients. Seventeen studies reported
survival to hospital discharge, with a cumulative survival rate of 534 of 1,529, and a range of 20.8% to 65.4%. Analyses encompassed 192 to 1,452 patients depending on the specific complication analyzed. The pooled estimate rates of complications with 95% confidence intervals were as follows: lower extremity ischemia, 16.9% (12.5% to 22.6%); fasciotomy or compartment syndrome, 10.3% (7.3% to 14.5%); lower extremity amputation, 4.7% (2.3% to 9.3%); stroke, 5.9% (4.2% to 8.3%); neurologic complications, 13.3% (9.9% to 17.7%); acute kidney injury, 55.6% (35.5% to 74.0%); renal replacement therapy, 46.0% (36.7% to 55.5%); major or significant bleeding, 40.8% (26.8% to 56.6%); rethoracotomy for bleeding or tamponade in postcardiotomy patients, 41.9% (24.3% to 61.8%); and significant infection, 30.4% (19.5% to 44.0%). Conclusions. Although ECMO can improve survival of patients with advanced heart disease, there is significant associated morbidity with performance of this intervention. These findings should be incorporated in the risk–benefit analysis when initiation of ECMO for cardiogenic shock is being considered.
V
circulatory support or transplant [11], as an assist to cardiopulmonary resuscitation [12, 13], for refractory cardiac arrest [14], for primary graft failure, and for secondary cardiac transplant rejection [15], among other indications. Although several small series have reported on complications associated with ECMO use in cardiogenic shock and cardiac arrest, the exact rates of these complications are also not well understood as they vary between series in part because of small study sizes [1, 3–5, 9, 16, 17]. In the absence of large clinical trials, performance of pooled analysis represents the best method for ascertaining complication rates associated with ECMO in cardiogenic shock and cardiac arrest.
enoarterial extracorporeal membrane oxygenation (ECMO) has been used successfully for cardiogenic shock and cardiac arrest refractory to usual resuscitative techniques as a form of mechanical support. Since it was first described four decades ago, the technology has been used for various cardiac diseases complicated by cardiac failure including postcardiotomy cardiogenic shock [1–7], fulminant myocarditis [8], acute coronary syndrome [9, 10], as a bridge to durable mechanical
Accepted for publication Sept 4, 2013. Address correspondence to Dr Azarbal, 8536 Wilshire Blvd #302, Los Angeles, CA 90211; e-mail: [email protected].
Ó 2014 by The Society of Thoracic Surgeons Published by Elsevier Inc
(Ann Thorac Surg 2014;97:610–6) Ó 2014 by The Society of Thoracic Surgeons
0003-4975/$36.00 http://dx.doi.org/10.1016/j.athoracsur.2013.09.008
Material and Methods Study Selection A systematic PubMed search using the terms ECMO, ECLS (extracorporeal life support), extracorporeal membrane oxygenation, and extracorporeal life support crossreferenced with the terms cardiac shock, cardiogenic shock, cardiopulmonary resuscitation, and cardiac arrest was conducted to reveal 959 papers, updated until November 14, 2012. In an attempt to keep the pooled analysis current, only studies published in the year 2000 and onward were included. Studies not accessible in the English language were excluded.
End Point Definitions The primary end points are reported rates of complications of lower limb ischemia, lower limb ischemia requiring fasciotomy or compartment syndrome, lower extremity ischemia requiring amputation, stroke, neurologic complications, acute kidney injury, renal replacement therapy, major or significant bleeding, rethoracotomy for bleeding or tamponade, and significant infection.
CHENG ET AL COMPLICATIONS OF ECMO
611
192 to 1,452 patients depending on the specific complication analyzed. The results are summarized in Table 2 and Figure 1. Seventeen studies reported survival to hospital discharge, with a cumulative survival rate of 534 of 1,529, and a range of 20.8% to 65.4%. Study populations were summarized into four categories based on indications for ECMO placement: postcardiotomy cardiogenic shock, cardiac arrest, acute myocardial infarction, and mixed populations. Nine studies reported survival to hospital discharge for postcardiotomy cardiogenic shock, with a cumulative survival rate of 386 of 1,150, and a range of 24.8% to 63.2%. One study reported on cardiac arrest with a survival rate of 16 of 77. One study reported on acute myocardial infarction with a survival rate of 16 of 27. Six studies reported on mixed populations, with a cumulative survival rate of 116 of 275, and a range of 25.0% to 65.4%.
Vascular Complications
Studies were included for each analysis if they reported rates of complications for venoarterial ECMO used for cardiogenic shock or cardiac arrest on 10 or more patients. Studies that reported only on an adult study population were included. If age ranges were reported, studies were included that reported on age at least 18 years old. For studies that met these inclusion and exclusion criteria but contained overlapping patients (same medical center, overlapping indications, overlapping dates), smaller studies reporting on fewer complications were excluded. For the rates of lower extremity ischemia, lower extremity fasciotomy or compartment syndrome, and lower extremity amputation, studies must also report the number of patients who underwent femoral cannulation, as we tend to agree with Rastan and colleagues [4] and Bisdas and associates [18] that lower limb ischemia (and its associated complications) is more unique to femoral arterial cannulation. Lastly, for rates of rethoracotomy for bleeding or tamponade, only postcardiotomy patients were included. Rates of less routinely reported complications that are not amenable to pooled analysis are also reported separately.
Thirteen studies were included in the analysis of lower extremity ischemia encompassing 677 patients. One study defined lower extremity ischemia as pulselessness, pallor, and gangrene [19]. The remaining studies did not define the complication [1, 3, 4, 7, 10, 17, 20–25]. The cumulative rate of lower extremity ischemia is 112 of 667 with a pooled estimate rate of 16.9% and a 95% confidence interval of 12.5% to 22.6%. Five studies were included in the analysis of lower extremity fasciotomy or compartment syndrome encompassing 335 patients. Four of five studies referred to the complication as fasciotomy attributable to either ischemia or compartment syndrome [1, 4, 9, 20], with the remaining study referring to the complication as compartment syndrome [3]. The cumulative rate of lower extremity fasciotomy or compartment syndrome is 33 of 335 with a pooled estimate rate of 10.3% and a 95% confidence interval of 7.3% to 14.5%. Five studies were included in the analysis of lower extremity amputation encompassing 192 patients [1, 3, 9, 20, 22]. The cumulative rate of lower extremity amputation is 7 of 192 with a pooled estimate rate of 4.7% and a 95% confidence interval of 2.3% to 9.3%. The use of distal leg perfusion cannulas was not uniformly reported. However, one study of 517 patients reported a decrease in leg ischemia and leg fasciotomy with the use of distal cannulation [4].
Statistical Analysis
Neurologic Complications
Cochran’s Q and I-squared values for heterogeneity are reported. A more conservative random-effects model was used for all analyses. Statistics were performed in Comprehensive Meta Analysis Version 2.2 (Biostat, Englewood, NJ), a commercially available meta-analysis statistical software.
Three studies were included in the analysis of stroke encompassing 630 patients. Two studies defined stroke as cerebral stroke or cerebral stroke and hemorrhage [4, 5], and the remaining study did not define the complication [20]. The cumulative rate of stroke is 36 of 630 with a pooled estimate rate of 5.9% and a 95% confidence interval of 4.2% to 8.3%. Nine studies were included in the analysis of neurologic complications encompassing 1,019 patients. The cumulative rate of neurologic complications is 151 of 1,019 with a pooled estimate rate of 13.3% and a 95%
Inclusion and Exclusion Criteria
Results Twenty studies were included in the analyses encompassing 1,866 patients (Table 1). Analyses encompassed
ADULT CARDIAC
Ann Thorac Surg 2014;97:610–6
ADULT CARDIAC
612
Study Bakhtiary et al [1] Belle et al [20] Bermudez et al [9] Elsharkawy et al [2] Hei et al [19] Hsu et al [3] Kagawa et al [21] Kim et al [10] Loforte et al [17] Moraca et al [22] Pagani et al [11] Rastan et al [4] Schmidt et al [27] Slottosch et al [23] Smith et al [24] Unosawa et al [25] Wang et al [5] Wu et al [6] Wu et al [13] Zhang et al [7]
Number of Patients
Patient Type
Average Age (y)
Age Range (y)
Males (%)
45 51 42 233
PCCS Mixed Mixed PCCS
60.1 13.6 51 15 53.5 57
Adults 18 28–80 Adults
78 75 83 67
29 51 37 156
68 51 77 27 73 26 33 517 220 77 17 47 62 110 60 32
PCCS PCCS CA AMI Mixed Mixed Mixed PCCS Mixed Mixed PCCS PCCS PCCS PCCS Mixed PCCS
49.2 13.3 63 15.7 61.9 63.7 11 60.3 11.6 57 47 11 63.5 11.2 49 16 60 13 66.6 13.6 64.4 12.5 51 15 60 14 51.33 55.4 11.9
18 Adults 18–74 45–81 23–84 18–76 Adults 18–84 Adults 25–83 37–83 22–83 Adults Adults 19–83 30–75
76 71 71 59 75 69 70 72 67 77 76 74 52 71 67 56
67 51 77 27 73 24 22 141
Peripheral ECMO (n, %) (64) (100) (88) (67)
(99) (100) (100) (100) (100) (92) (67) (27) – – 11 (65) 32 (68) – – – 17 (53)
IABP (n, %)
Average Time on ECMO (h)
Survival to D/C (n, %)
(67) (10) (88) (9.4)
153.6 – 67.1 –
13 (28.9) 14 (27.5) – 84 (36.1)
11 (16) – 52 (68) 2 (7) 73 (100) 21 (80) 20 (61) 383 (74) – 72 (94) 14 (82) 39 (83) 19 (31) – 44 (73) –
114.6 180 – 30.2 261.6 72 65 78.7 320.9 79 86 63.5 61 143.3 97.3 64.8
30 5 37 22
43 17 16 16 33 17 12 128
7 14 34 46 32 8
(63.2) (33.3) (20.8) (59.3) (45.2) (65.4) (36.4) (24.8) – – (41.2) (29.8) (54.8) (41.8) (53.3) (25.0)
Bridged to VAD (n, %)/Survival to D/C (n, %) 5 (11.1)/3 (60) – 22 (52.4)/– –
4 3 9 10 15
– – (5.2)/– – (4.1)/2 (66.7) (34.6)/6 (66.7) (30.3)/8 (80) (2.9)/3 (20) – – – – – – – –
Bridged to HTP (n, %)/Survival to D/C (n, %)
CHENG ET AL COMPLICATIONS OF ECMO
Table 1. Studies Included in Analysis: Baseline Characteristics
2 (4.4)/1 (50) – – – 8 (11.8)/6 (75) 3 (5.9)/3 (100) – – 0 (0)/N/A 1 (3.8)/1 (100) 7 (21.2)/7 (100) 5 (1)/2 (40) – – – – – – 3 (5)/2 (66.7) –
ACS ¼ acute coronary syndrome; AMI ¼ acute myocardial infarction; CA ¼ cardiac arrest; D/C ¼ hospital discharge; ECMO ¼ extracorporeal membrane oxygenation; HTP ¼ heart transplant; IABP ¼ intraaortic balloon pump; Mixed ¼ mixed population; N/A ¼ not applicable; PCCS ¼ postcardiotomy cardiogenic shock; VAD ¼ ventricular assist device.
Ann Thorac Surg 2014;97:610–6
LEA ¼ lower extremity amputation; RRT ¼ renal replacement therapy.
LEF ¼ lower extremity fasciotomy or compartment syndrome;
613
confidence interval of 9.9% to 17.7%. Three of nine studies included hemorrhage and ischemic stroke under neurologic complications [1, 3, 5]. Another two of nine studies chose a broader definition to include complications such as coma, diffuse anoxic brain injury, and brain death [19, 23]. The remaining four of nine studies either referred to neurologic complications as “brain damage” or did not define the complication [4, 6, 9, 25].
Renal Injury Fifteen studies were included in the analysis of renal replacement therapy encompassing 1,452 patients. All studies referred to renal replacement therapy as postECMO rates [1–6, 9–11, 13, 17, 20, 22, 23, 25]. The cumulative rate of renal replacement therapy after ECMO is 758 of 1,452 with a pooled estimate rate of 46.0% and a 95% confidence interval of 36.7% to 55.5%. Six studies were included in the analysis of acute kidney injury encompassing 380 patients. The cumulative rate of acute kidney injury is 197 of 380 with a pooled estimate rate of 55.6% and a 95% confidence interval of 35.5% to 74.0%. Four of six studies did not define the complication [1, 5, 21, 23], one study defined renal injury as creatinine elevation of 130 mmol/L or dialysis [19], and a final study defined renal injury as a greater than 25% increase in creatinine if renal function was normal at baseline or a greater than 1 mg/dL increase in creatinine if renal function was abnormal at baseline [3].
Bleeding Five studies were included in the analysis of major or significant bleeding encompassing 260 patients. One study each referred to the complication as major bleeding, massive bleeding, severe bleeding, bleeding and hematoma, or bleeding and tamponade [7, 10, 17, 20, 21]. The cumulative rate of major or significant bleeding is 120 of 260 with a pooled estimate rate of 40.8% and a 95% confidence interval of 26.8% to 56.6%. Six studies were included in the analysis of rethoracotomy for bleeding or tamponade, encompassing 828 postcardiotomy patients. All studies defined the complication as rethoracotomy or surgical exploration of the thoracic cavity for bleeding or tamponade [1, 4–6, 23, 24]. The cumulative rate of rethoracotomy for bleeding or tamponade is 409 of 828 with a pooled estimate rate of 41.9% and a 95% confidence interval of 24.3% to 61.8%. For six studies that reported on the average number of units of packed red blood cells transfused, the values ranged from 12.7 to 29.0 units [5, 16, 17, 23, 24, 26].
Infection Ten studies were included in the analysis of significant infection encompassing 922 patients. The cumulative rate of significant infection is 321 of 922 with a pooled estimate rate of 30.4% and a 95% confidence interval of 19.5% to 44.0%. All studies referred to infection as post-ECMO rates. Eight studies defined the complication as sepsis or suspected sepsis requiring antibiotics use [1–3, 5, 17, 19, 20, 23], with four of eight studies additionally requiring positive blood cultures. Another study defined
ADULT CARDIAC
LEI ¼ lower extremity ischemia;
Re-Thx ¼ rethoracotomy for
CHENG ET AL COMPLICATIONS OF ECMO
AKI ¼ acute kidney injury; bleeding or tamponade;
12.5–22.6 7.3–14.5 2.3–9.3 4.2–8.3 9.9–17.7 35.5–74.0 36.7–55.5 26.8–56.6 24.3–61.8 19.5–44.0 16.9 10.3 4.7 5.9 13.3 55.6 46.0 40.8 41.9 30.4 0.004 0.350 0.658 0.346 0.018
Complications of Extracorporeal Membrane Oxygenation for Treatment of Cardiogenic Shock and Cardiac Arrest: A Meta-Analysis of 1,866 Adult Patients Richard Cheng, MD, Rory Hachamovitch, MD, Michelle Kittleson, MD, PhD, Jignesh Patel, MD, PhD, Francisco Arabia, MD, Jaime Moriguchi, MD, Fardad Esmailian, MD, and Babak Azarbal, MD Cedars-Sinai Heart Institute, Los Angeles, California, and Department of Cardiovascular Medicine, Heart and Vascular Institute, Cleveland Clinic, Cleveland, Ohio
Background. Venoarterial extracorporeal membrane oxygenation (ECMO) has been used successfully for treatment of cardiogenic shock or cardiac arrest. The exact complication rate is not well understood, in part because of small study sizes. In the absence of large clinical trials, performance of pooled analysis represents the best method for ascertaining complication rates for ECMO. Methods. A systematic PubMed search was conducted on ECMO for treatment of cardiogenic shock or cardiac arrest in adult patients only, updated to November 2012. Studies with more than 10 patients published in the year 2000 or later that reported complication rates for ECMO were included. Specific complications analyzed included lower extremity ischemia, fasciotomy or compartment syndrome, amputation, stroke, neurologic complications, acute kidney injury, renal replacement therapy, major or significant bleeding, rethoracotomy for bleeding or tamponade, and significant infection. For studies that included overlapping patients, the largest study was included and the others excluded. Cochran’s Q and I-squared were calculated. A more conservative randomeffects model was chosen for all analyses. Results. Twenty studies were included in the analyses encompassing 1,866 patients. Seventeen studies reported
survival to hospital discharge, with a cumulative survival rate of 534 of 1,529, and a range of 20.8% to 65.4%. Analyses encompassed 192 to 1,452 patients depending on the specific complication analyzed. The pooled estimate rates of complications with 95% confidence intervals were as follows: lower extremity ischemia, 16.9% (12.5% to 22.6%); fasciotomy or compartment syndrome, 10.3% (7.3% to 14.5%); lower extremity amputation, 4.7% (2.3% to 9.3%); stroke, 5.9% (4.2% to 8.3%); neurologic complications, 13.3% (9.9% to 17.7%); acute kidney injury, 55.6% (35.5% to 74.0%); renal replacement therapy, 46.0% (36.7% to 55.5%); major or significant bleeding, 40.8% (26.8% to 56.6%); rethoracotomy for bleeding or tamponade in postcardiotomy patients, 41.9% (24.3% to 61.8%); and significant infection, 30.4% (19.5% to 44.0%). Conclusions. Although ECMO can improve survival of patients with advanced heart disease, there is significant associated morbidity with performance of this intervention. These findings should be incorporated in the risk–benefit analysis when initiation of ECMO for cardiogenic shock is being considered.
V
circulatory support or transplant [11], as an assist to cardiopulmonary resuscitation [12, 13], for refractory cardiac arrest [14], for primary graft failure, and for secondary cardiac transplant rejection [15], among other indications. Although several small series have reported on complications associated with ECMO use in cardiogenic shock and cardiac arrest, the exact rates of these complications are also not well understood as they vary between series in part because of small study sizes [1, 3–5, 9, 16, 17]. In the absence of large clinical trials, performance of pooled analysis represents the best method for ascertaining complication rates associated with ECMO in cardiogenic shock and cardiac arrest.
enoarterial extracorporeal membrane oxygenation (ECMO) has been used successfully for cardiogenic shock and cardiac arrest refractory to usual resuscitative techniques as a form of mechanical support. Since it was first described four decades ago, the technology has been used for various cardiac diseases complicated by cardiac failure including postcardiotomy cardiogenic shock [1–7], fulminant myocarditis [8], acute coronary syndrome [9, 10], as a bridge to durable mechanical
Accepted for publication Sept 4, 2013. Address correspondence to Dr Azarbal, 8536 Wilshire Blvd #302, Los Angeles, CA 90211; e-mail: [email protected].
Ó 2014 by The Society of Thoracic Surgeons Published by Elsevier Inc
(Ann Thorac Surg 2014;97:610–6) Ó 2014 by The Society of Thoracic Surgeons
0003-4975/$36.00 http://dx.doi.org/10.1016/j.athoracsur.2013.09.008
Material and Methods Study Selection A systematic PubMed search using the terms ECMO, ECLS (extracorporeal life support), extracorporeal membrane oxygenation, and extracorporeal life support crossreferenced with the terms cardiac shock, cardiogenic shock, cardiopulmonary resuscitation, and cardiac arrest was conducted to reveal 959 papers, updated until November 14, 2012. In an attempt to keep the pooled analysis current, only studies published in the year 2000 and onward were included. Studies not accessible in the English language were excluded.
End Point Definitions The primary end points are reported rates of complications of lower limb ischemia, lower limb ischemia requiring fasciotomy or compartment syndrome, lower extremity ischemia requiring amputation, stroke, neurologic complications, acute kidney injury, renal replacement therapy, major or significant bleeding, rethoracotomy for bleeding or tamponade, and significant infection.
CHENG ET AL COMPLICATIONS OF ECMO
611
192 to 1,452 patients depending on the specific complication analyzed. The results are summarized in Table 2 and Figure 1. Seventeen studies reported survival to hospital discharge, with a cumulative survival rate of 534 of 1,529, and a range of 20.8% to 65.4%. Study populations were summarized into four categories based on indications for ECMO placement: postcardiotomy cardiogenic shock, cardiac arrest, acute myocardial infarction, and mixed populations. Nine studies reported survival to hospital discharge for postcardiotomy cardiogenic shock, with a cumulative survival rate of 386 of 1,150, and a range of 24.8% to 63.2%. One study reported on cardiac arrest with a survival rate of 16 of 77. One study reported on acute myocardial infarction with a survival rate of 16 of 27. Six studies reported on mixed populations, with a cumulative survival rate of 116 of 275, and a range of 25.0% to 65.4%.
Vascular Complications
Studies were included for each analysis if they reported rates of complications for venoarterial ECMO used for cardiogenic shock or cardiac arrest on 10 or more patients. Studies that reported only on an adult study population were included. If age ranges were reported, studies were included that reported on age at least 18 years old. For studies that met these inclusion and exclusion criteria but contained overlapping patients (same medical center, overlapping indications, overlapping dates), smaller studies reporting on fewer complications were excluded. For the rates of lower extremity ischemia, lower extremity fasciotomy or compartment syndrome, and lower extremity amputation, studies must also report the number of patients who underwent femoral cannulation, as we tend to agree with Rastan and colleagues [4] and Bisdas and associates [18] that lower limb ischemia (and its associated complications) is more unique to femoral arterial cannulation. Lastly, for rates of rethoracotomy for bleeding or tamponade, only postcardiotomy patients were included. Rates of less routinely reported complications that are not amenable to pooled analysis are also reported separately.
Thirteen studies were included in the analysis of lower extremity ischemia encompassing 677 patients. One study defined lower extremity ischemia as pulselessness, pallor, and gangrene [19]. The remaining studies did not define the complication [1, 3, 4, 7, 10, 17, 20–25]. The cumulative rate of lower extremity ischemia is 112 of 667 with a pooled estimate rate of 16.9% and a 95% confidence interval of 12.5% to 22.6%. Five studies were included in the analysis of lower extremity fasciotomy or compartment syndrome encompassing 335 patients. Four of five studies referred to the complication as fasciotomy attributable to either ischemia or compartment syndrome [1, 4, 9, 20], with the remaining study referring to the complication as compartment syndrome [3]. The cumulative rate of lower extremity fasciotomy or compartment syndrome is 33 of 335 with a pooled estimate rate of 10.3% and a 95% confidence interval of 7.3% to 14.5%. Five studies were included in the analysis of lower extremity amputation encompassing 192 patients [1, 3, 9, 20, 22]. The cumulative rate of lower extremity amputation is 7 of 192 with a pooled estimate rate of 4.7% and a 95% confidence interval of 2.3% to 9.3%. The use of distal leg perfusion cannulas was not uniformly reported. However, one study of 517 patients reported a decrease in leg ischemia and leg fasciotomy with the use of distal cannulation [4].
Statistical Analysis
Neurologic Complications
Cochran’s Q and I-squared values for heterogeneity are reported. A more conservative random-effects model was used for all analyses. Statistics were performed in Comprehensive Meta Analysis Version 2.2 (Biostat, Englewood, NJ), a commercially available meta-analysis statistical software.
Three studies were included in the analysis of stroke encompassing 630 patients. Two studies defined stroke as cerebral stroke or cerebral stroke and hemorrhage [4, 5], and the remaining study did not define the complication [20]. The cumulative rate of stroke is 36 of 630 with a pooled estimate rate of 5.9% and a 95% confidence interval of 4.2% to 8.3%. Nine studies were included in the analysis of neurologic complications encompassing 1,019 patients. The cumulative rate of neurologic complications is 151 of 1,019 with a pooled estimate rate of 13.3% and a 95%
Inclusion and Exclusion Criteria
Results Twenty studies were included in the analyses encompassing 1,866 patients (Table 1). Analyses encompassed
ADULT CARDIAC
Ann Thorac Surg 2014;97:610–6
ADULT CARDIAC
612
Study Bakhtiary et al [1] Belle et al [20] Bermudez et al [9] Elsharkawy et al [2] Hei et al [19] Hsu et al [3] Kagawa et al [21] Kim et al [10] Loforte et al [17] Moraca et al [22] Pagani et al [11] Rastan et al [4] Schmidt et al [27] Slottosch et al [23] Smith et al [24] Unosawa et al [25] Wang et al [5] Wu et al [6] Wu et al [13] Zhang et al [7]
Number of Patients
Patient Type
Average Age (y)
Age Range (y)
Males (%)
45 51 42 233
PCCS Mixed Mixed PCCS
60.1 13.6 51 15 53.5 57
Adults 18 28–80 Adults
78 75 83 67
29 51 37 156
68 51 77 27 73 26 33 517 220 77 17 47 62 110 60 32
PCCS PCCS CA AMI Mixed Mixed Mixed PCCS Mixed Mixed PCCS PCCS PCCS PCCS Mixed PCCS
49.2 13.3 63 15.7 61.9 63.7 11 60.3 11.6 57 47 11 63.5 11.2 49 16 60 13 66.6 13.6 64.4 12.5 51 15 60 14 51.33 55.4 11.9
18 Adults 18–74 45–81 23–84 18–76 Adults 18–84 Adults 25–83 37–83 22–83 Adults Adults 19–83 30–75
76 71 71 59 75 69 70 72 67 77 76 74 52 71 67 56
67 51 77 27 73 24 22 141
Peripheral ECMO (n, %) (64) (100) (88) (67)
(99) (100) (100) (100) (100) (92) (67) (27) – – 11 (65) 32 (68) – – – 17 (53)
IABP (n, %)
Average Time on ECMO (h)
Survival to D/C (n, %)
(67) (10) (88) (9.4)
153.6 – 67.1 –
13 (28.9) 14 (27.5) – 84 (36.1)
11 (16) – 52 (68) 2 (7) 73 (100) 21 (80) 20 (61) 383 (74) – 72 (94) 14 (82) 39 (83) 19 (31) – 44 (73) –
114.6 180 – 30.2 261.6 72 65 78.7 320.9 79 86 63.5 61 143.3 97.3 64.8
30 5 37 22
43 17 16 16 33 17 12 128
7 14 34 46 32 8
(63.2) (33.3) (20.8) (59.3) (45.2) (65.4) (36.4) (24.8) – – (41.2) (29.8) (54.8) (41.8) (53.3) (25.0)
Bridged to VAD (n, %)/Survival to D/C (n, %) 5 (11.1)/3 (60) – 22 (52.4)/– –
4 3 9 10 15
– – (5.2)/– – (4.1)/2 (66.7) (34.6)/6 (66.7) (30.3)/8 (80) (2.9)/3 (20) – – – – – – – –
Bridged to HTP (n, %)/Survival to D/C (n, %)
CHENG ET AL COMPLICATIONS OF ECMO
Table 1. Studies Included in Analysis: Baseline Characteristics
2 (4.4)/1 (50) – – – 8 (11.8)/6 (75) 3 (5.9)/3 (100) – – 0 (0)/N/A 1 (3.8)/1 (100) 7 (21.2)/7 (100) 5 (1)/2 (40) – – – – – – 3 (5)/2 (66.7) –
ACS ¼ acute coronary syndrome; AMI ¼ acute myocardial infarction; CA ¼ cardiac arrest; D/C ¼ hospital discharge; ECMO ¼ extracorporeal membrane oxygenation; HTP ¼ heart transplant; IABP ¼ intraaortic balloon pump; Mixed ¼ mixed population; N/A ¼ not applicable; PCCS ¼ postcardiotomy cardiogenic shock; VAD ¼ ventricular assist device.
Ann Thorac Surg 2014;97:610–6
LEA ¼ lower extremity amputation; RRT ¼ renal replacement therapy.
LEF ¼ lower extremity fasciotomy or compartment syndrome;
613
confidence interval of 9.9% to 17.7%. Three of nine studies included hemorrhage and ischemic stroke under neurologic complications [1, 3, 5]. Another two of nine studies chose a broader definition to include complications such as coma, diffuse anoxic brain injury, and brain death [19, 23]. The remaining four of nine studies either referred to neurologic complications as “brain damage” or did not define the complication [4, 6, 9, 25].
Renal Injury Fifteen studies were included in the analysis of renal replacement therapy encompassing 1,452 patients. All studies referred to renal replacement therapy as postECMO rates [1–6, 9–11, 13, 17, 20, 22, 23, 25]. The cumulative rate of renal replacement therapy after ECMO is 758 of 1,452 with a pooled estimate rate of 46.0% and a 95% confidence interval of 36.7% to 55.5%. Six studies were included in the analysis of acute kidney injury encompassing 380 patients. The cumulative rate of acute kidney injury is 197 of 380 with a pooled estimate rate of 55.6% and a 95% confidence interval of 35.5% to 74.0%. Four of six studies did not define the complication [1, 5, 21, 23], one study defined renal injury as creatinine elevation of 130 mmol/L or dialysis [19], and a final study defined renal injury as a greater than 25% increase in creatinine if renal function was normal at baseline or a greater than 1 mg/dL increase in creatinine if renal function was abnormal at baseline [3].
Bleeding Five studies were included in the analysis of major or significant bleeding encompassing 260 patients. One study each referred to the complication as major bleeding, massive bleeding, severe bleeding, bleeding and hematoma, or bleeding and tamponade [7, 10, 17, 20, 21]. The cumulative rate of major or significant bleeding is 120 of 260 with a pooled estimate rate of 40.8% and a 95% confidence interval of 26.8% to 56.6%. Six studies were included in the analysis of rethoracotomy for bleeding or tamponade, encompassing 828 postcardiotomy patients. All studies defined the complication as rethoracotomy or surgical exploration of the thoracic cavity for bleeding or tamponade [1, 4–6, 23, 24]. The cumulative rate of rethoracotomy for bleeding or tamponade is 409 of 828 with a pooled estimate rate of 41.9% and a 95% confidence interval of 24.3% to 61.8%. For six studies that reported on the average number of units of packed red blood cells transfused, the values ranged from 12.7 to 29.0 units [5, 16, 17, 23, 24, 26].
Infection Ten studies were included in the analysis of significant infection encompassing 922 patients. The cumulative rate of significant infection is 321 of 922 with a pooled estimate rate of 30.4% and a 95% confidence interval of 19.5% to 44.0%. All studies referred to infection as post-ECMO rates. Eight studies defined the complication as sepsis or suspected sepsis requiring antibiotics use [1–3, 5, 17, 19, 20, 23], with four of eight studies additionally requiring positive blood cultures. Another study defined
ADULT CARDIAC
LEI ¼ lower extremity ischemia;
Re-Thx ¼ rethoracotomy for
CHENG ET AL COMPLICATIONS OF ECMO
AKI ¼ acute kidney injury; bleeding or tamponade;
12.5–22.6 7.3–14.5 2.3–9.3 4.2–8.3 9.9–17.7 35.5–74.0 36.7–55.5 26.8–56.6 24.3–61.8 19.5–44.0 16.9 10.3 4.7 5.9 13.3 55.6 46.0 40.8 41.9 30.4 0.004 0.350 0.658 0.346 0.018
