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Outcome of in-hospital adult cardiopulmonary resuscitation assisted with portable auto-priming percutaneous cardiopulmonary support
International Journal of Cardiology 151 (2011) 12–17
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International Journal of Cardiology j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / i j c a r d
Outcome of in-hospital adult cardiopulmonary resuscitation assisted with portable auto-priming percutaneous cardiopulmonary support Ik Joon Jo a,1, Tae Gun Shin a,1, Min Sub Sim a, Hyoung Gon Song a, Yeon Kwon Jeong a, Yong-Bien Song b, Joo-Yong Hahn b, Seung Hyuk Choi b, Hyeon-Cheol Gwon b, Eun-Seok Jeon b, Wook Sung Kim c, Young Tak Lee c, Kiick Sung c,⁎, Jin-Ho Choi a,b,⁎ a b c
Departments of Emergency Medicine, Cardiac and Vascular Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea Medicine, Cardiac and Vascular Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea Thoracic Surgery, Cardiac and Vascular Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
a r t i c l e
i n f o
Article history: Received 9 July 2009 Received in revised form 17 November 2009 Accepted 17 April 2010 Available online 15 May 2010 Keywords: Percutaneous cardiopulmonary support Cardiopulmonary resuscitation Percutaneous cardiopulmonary support Cardiopulmonary resuscitation In-hospital cardiac arrest
a b s t r a c t Background: Outcome from in-hospital cardiopulmonary resuscitation (CPR) is still unsatisfactory. CPR assisted with percutaneous cardiopulmonary support (PCPS) is expected to improve the outcome of inhospital CPR. Methods: We retrospectively analyzed 83 consecutive cases of adult in-hospital CPR assisted by a portable pre-assembled auto-priming PCPS system (EBS, Terumo, Japan) from January 2004 to December 2007. Results: PCPS was successfully performed in 97.6% of the patients and could be weaned in 57.8% of the patients. The survival-to-discharge rate was 41.0% with an acceptable neurological status in 85.3% of the patients. The 6-month survival was 38.6%. Survival-to-discharge decreased about 1% for each 1 min increase in the duration of CPR. The probability of survival was about 65%, 45%, and 19% when the duration of CPR was 10, 30, or 60 min, respectively. Multivariate analysis adjusted with clinical factors including organ dysfunction severity scores revealed that defibrillation and CPR duration less than 35 min were independent predictors for both survival-to-discharge (odds ratio = 8.0, 95% CI = 2.8–23.0, p b 0.001) and 6-month survival (hazard ratio = 3.3, 95% CI = 1.9–5.9, p b 0.001). Conclusions: Our results showed that CPR assisted with PCPS results in an acceptable survival-to-discharge rate and mid-term prognosis. © 2010 Elsevier Ireland Ltd. All rights reserved.
1. Introduction The overall survival rate of patients who experience in-hospital cardiac arrest remains unsatisfactory [1,2]. For example, large-scale nationwide registries conducted in United States and Taiwan showed that the survival rate of patients who required in-hospital CPR was 17 to 18% despite a median defibrillation time of less than 1 min [3,4]. Even when the resumption of spontaneous circulation (ROSC) is achieved after CPR, the survival-to-discharge rate is only 29 to 33% and has not changed significantly in the past half-century [5–7]. One of the greatest limitations of CPR is the very narrow time window of
⁎ Corresponding authors. Choi is to be contacted Department of Emergency Medicine, Department of Medicine, Chest Pain Center, Cardiac and Vascular Center, Samsung Medical Center, 50 Irwon-dong, Gangnam-ku, Seoul, 135-710, Republic of Korea. Tel.: +82 2 3410 3419; fax: +82 2 3410 3849. Sung, Department of Thoracic Surgery, Cardiac and Vascular Center, Samsung Medical Center. 50 Irwon-dong, Gangnam-ku, Seoul, 135-710, Republic of Korea. Tel.: +82 2 3410 6849; fax: +82 2 3410 6541. E-mail addresses: [email protected] (K. Sung), [email protected] (J.-H. Choi). 1 Both authors equally contributed to this work. 0167-5273/$ – see front matter © 2010 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijcard.2010.04.050
effectiveness. Most studies showed that a CPR duration of more than 20 min has resulted in a survival rate of less than 5% [3,4,8]. Mechanical support of the cardiopulmonary system has been attempted to improve the result of CPR [9]. Extracorporeal membrane oxygenation (ECMO), which is composed of a centrifugal pump and a membranous artificial lung which provide hemodynamic support, has shown promising outcomes in recent clinical investigations [10–12]. The percutaneous cardiopulmonary support (PCPS) is a portable preassembled heparin-coated ECMO system that can be primed immediately and applied percutaneously in emergency situations [13,14]. We have used PCPS as an adjunct to conventional CPR and post-resuscitation care since 2004 [15]. We investigated the outcomes and mid-term survival of patients who suffered in-hospital cardiac arrest and were treated by CPR assisted with PCPS. 2. Methods 2.1. Study subjects Between January 2004 and December 2007, 164 cases of emergency PCPS have been performed on patients with intractable cardiogenic shock without cardiac arrest or cardiac arrest at Samsung Medical Center, a 1900-bed tertiary academic hospital in urban area.
I.J. Jo et al. / International Journal of Cardiology 151 (2011) 12–17 Patients on PCPS for hemodynamic support without CPR and those who previously received it before CPR were excluded (n=62). Pediatric patients, who were younger than 15 years, also excluded (n=19). After accounting for these exclusions, we retrospectively reviewed the medical records of 83 adult patients who suffered a cardiac arrest, and received PCPS during CPR or within at least 6 h immediately after ROSC. The institutional review board of the Samsung Medical Center approved the study protocol. A CPR event was defined as the loss of a palpable or monitored pulse and the loss of respiration despite aggressive medical therapy which required the application of chest compressions. The CPR duration was defined as the interval between the initiation of CPR and the initiation of PCPS when it was performed before successful ROSC, or the duration of chest compressions when it was used after ROSC [11]. ROSC was defined as the return of a spontaneous heartbeat with a detectable peripheral arterial pulsation. Because patients with PCPS were frequently dependent on artificial circulation, ROSC was confirmed after brief reduction of PCPS flow. 2.2. CPR and ECMO teams The CPR team consists of emergency physicians certified in advanced cardiac lifesupport, as well as nurses and paramedics. They responded to most cases of in-hospital cardiac arrest, except cases in the intensive care unit which were treated by intensivists. The PCPS team consists of experienced interventional cardiologists, cardiovascular surgeons, and paramedics. CPR team leader called the PCPS team in the following conditions; when there was no ROSC after 10 min of CPR, when ROSC could not be maintained for more than 20 min, or when the patient could not be expected to recover due to underlying severe left ventricular dysfunction or coronary artery disease despite short CPR duration less than 10 min. During the postresuscitation period after ROSC, the
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PCPS team was also called when cardiogenic shock was unresponsive to conventional measures, or when ventricular arrhythmia was refractory. In cases of patients with previously known severe irreversible brain damage, terminal malignancy, trauma with uncontrolled bleeding, and those who previously signed ‘do not attempt resuscitation’, the decisions for PCPS application were deterred. Verbal permission for the initiation of the PCPS was obtained from the relatives. Written informed consent was obtained later. Both CPR and PCPS teams were available at all times. PCPS was usually available within 10 min during the day. During night shifts or weekend, it was available within 10 to 20 min.
2.3. Procedures The Capiox Emergency Bypass System (EBS)™ (Terumo, Tokyo, Japan) was used in all cases (Fig. 1). The system consists of a portable extracorporeal life-support controller with internal back-up battery and a disposable bypass circuit integrated with a heparin-coated membrane oxygenator and centrifugal pump. Trained personnel are able to move the device to the bedside, connect saline fluid and oxygen lines, and start the device immediately. The system completed de-airing priming process automatically within 5 min. Device insertion was performed by attending interventional cardiologists or cardiovascular surgeons who were house staffs on duty. Physicians in their learning curve could perform the procedure under direct guidance of staffs after assistance for 6 months. Vascular cannulation was mostly done percutaneously using the Seldinger technique. Surgical exposure was performed in difficult cases, such as patients with peripheral artery disease or severe obesity. Vascular cannula size was 14 to 21 French for artery, and 21 to 28 French for vein. A catheter was inserted into the femoral artery to facilitate distal limb perfusion in the event of leg ischemia after arterial cannulation.
Fig. 1. A percutaneous cardiopulmonary support (PCPS), Terumo EBS. Panel A: A PCPS controller and accessories built in mobile cart. If necessary, the desktop computer-sized controller and other parts can be detached and carried by hands. Panel B: A disposable PCPS circuit with integrated pump and heparin-coated oxygenator, which was partially opened from aseptic package. Panel C: Scheme of PCPS support. A venous cannula located in right atrium and intravenous cava drains hypoxic venous blood. The blood is sent to arterial cannula by centrifugal pump after gas exchange at oxygenator.
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Anticoagulation was accomplished by a bolus injection of unfractionated heparin, which was followed by a continuous intravenous infusion of heparin to maintain the activated clotting time between 180 and 200 s. The flow rate was set above 2.2 L/min/body surface area (m2) initially, and was adjusted subsequently to maintain a mean arterial pressure above 65 mmHg. The partial pressure of arterial oxygen in the right arm was maintained at greater than 100 mmHg to ensure the sufficient oxygenation of the brain. Transfusion of red blood cell and fresh frozen plasma was performed to maintain intravascular volume which was essential to functional PCPS circuit, and to maintain hematocrit which was important to tissue oxygen delivery. Usually 5 to 7 units of red blood cell and 3 to 5 units of fresh frozen plasma were required within first 24 h. Detailed management was previously reported by us [15]. Daily echocardiograms were performed to evaluate the recovery of left ventricular function and to determine the potential for developing an intraventricular thrombus. Minimal dose of intravenous catecholamine was used to maintain a pulsatile arterial waveform and avoid the development of a left ventricular thrombus. Weaning off of the PCPS was considered when the patient was hemodynamically stable and adequately oxygenated under a low dose of intravenous catecholamines (dopamine or dobutamine of less than 5 μg/kg/min) and a PCPS flow of less than 1 L/min for more than 4 h. The PCPS circuit was removed when the patient was stable for more than 20 min with a PCPS flow rate of 0.5 L/min. If the femoral artery was atherosclerotic or a cannula larger than 21 French was used, the femoral arteriotomy site was surgically repaired. Otherwise, hemostasis could be achieved by prolonged manual compression. The femoral vein was closed using a simple percutaneous suture and manual compression. If the weaning was unsuccessful in 3 to 4 days, the disposable bypass circuit was replaced with a new circuit at the bedside, and a ventricular assist device or heart transplantation was considered in the absence of contraindications. The termination of PCPS was considered with the consent of the family of the patient when there was intractable multi-organ failure or severe neurologic damage consistent with a vegetative state or brain death. 2.4. Data collection and statistical analysis Clinical data was collected according to the modified guidelines for reviewing and reporting in-hospital resuscitations [16]. The severity of organ dysfunction was measured using the Simplified Acute Physiology Score (SAPS) II at the time of the arrest, and the maximum value of the Sequential Organ Failure Assessment (SOFA) during admission [17,18]. The neurological status of each patient at the time of discharge was assessed using the Glasgow–Pittsburgh cerebral-performance categories (CPC) score [19]. The primary endpoint was survival-to-discharge. Continuous variables were expressed as the mean± standard deviation or median with interquartile ranges, if necessary. Continuous and categorical variables were compared using Mann–Whitney U test or Fisher's exact test, respectively. A multivariate logistic regression model using forward conditional method was used to seek independent predictors of survival. The probability of survival according to the duration of CPR, which has been known to be one of most significant prognostic factors [8], was calculated according to the method of Chen [11]. Kaplan–Meier curve was plotted to show the trend of mid-term survival. SPSS version 13.0 (SPSS Inc., Chicago IL, USA) was used for the statistical analysis. A two-tailed P b 0.05 was considered statistically significant.
3. Results 3.1. CPR-related parameters The most common cause of cardiac arrest in this study was acute coronary syndrome (48.2%). The demographics and pre-existing comorbidities were similar between the in-hospital survivors (41.0%, N = 34) and non-survivors (59.0%, N = 49). Defibrillation was attempted in all patients who suffered from a ventricular tachyarrhythmia and two patients who had an undetermined rhythm (Table 1). The location or time zone of CPR was also not different between the inhospital survivors and non-survivors. CPR duration was shorter for the inhospital survivors compared to the non-survivors (24.0±17.9 min versus 46.4±27.6 min, pb 0.001). ROSC before a PCPS attempt was more common for the in-hospital survivors compared to the non-survivors (61.8% versus 26.5%, p=0.002). Organ dysfunction parameters in the first 24 h were not significantly different between the in-hospital survivors and non-survivors. However, lactate level was significantly lower in the in-hospital survivors compared to the non-survivors (7.1±4.4 mg/dL versus 11.8±5.9 mg/dL, p=0.002) (Table 2). 3.2. PCPS and in-hospital care parameters PCPS introduction was successful in 97.6% (81/83) of the patients. The two patients in whom it failed had severe peripheral artery
Table 1 Pre-CPR parameters.
N Age, mean ± SD Median (interquartile ranges) Male gender Pre-existing comorbidity Diabetes Hypertension Stroke Chronic renal failure Malignancy Lung insufficiency GI bleeding Causes of arrest Acute coronary syndrome Aggravation of heart failure Myocarditis Pulmonary thromboembolism Other circulatory obstructiona Primary arrhythmia Unknown Clinical situation Post any invasive procedure Post cardiac surgery Post noncardiac surgery Post cardiac catheterization
All
Survivor
Non-survivor p-value
83 (100) 58.1 ± 17.3 63 (48–70) 53 (63.9)
34 (41.0) 56.7 ± 16.3 62 (48–67) 21 (61.8)
49 (59.0) 59.1 ± 18.1 67 (50–71) 32 (65.3)
– 0.538 0.238 0.8
18 (21.7) 29 (34.9) 5 (6.0) 7 (8.4) 8 (9.6) 5 (6.0) 9 (10.8)
8 (20.0) 11 (32.4) 3 (8.8) 2 (5.9) 2 (5.9) 2 (5.9) 3 (8.8)
10 (23.3) 18 (36.7) 2 (4.1) 5 (10.2) 6 (12.2) 3 (6.1) 6 (12.2)
0.790 0.816 0.396 0.999 0.462 0.999 0.731
40 (48.2) 16 (19.3) 2 (2.4) 4 (4.8)
17 (50.0) 6 (17.6) 1 (2.9) 2 (5.9)
23 (46.9) 10 (20.4) 1 (2.0) 2 (4.1)
0.826 0.999 0.999 0.999
5 (6.0)
4 (11.8)
1 (2.0)
0.153
1 (1.2) 15 (18.1)
1 (2.9) 4 (11.8)
0 (0) 11 (22.4)
0.410 0.257
47 14 16 17
20 (58.8) 8 (23.5) 5 (14.7) 7 (20.6)
27 (55.1) 6 (12.2) 11 (22.4) 10 (20.4)
0.823 0.236 0.414 0.999
(56.6) (16.9) (19.3) (20.5)
Data shown as number (percent) or mean ± SD. p-value by Fisher's exact test or Mann– Whitney U-test, appropriately. a Pericardial tamponade and critical aortic stenosis. Primary arrhythmia includes one case of hypertrophic cardiomyopathy with ventricular fibrillation.
Table 2 CPR and post-CPR parameters.
CPR location Intensive care unita Catheterization lab Emergency room General ward CPR time zone 7 AM–5 PM 5 PM–11 PM 11 PM–7 AM Pre-arrest rhythm monitoring Asystole PEA VT or V-fib Defibrillation CPR duration (min) Median (interquartile ranges) ROSC before PCPS CPR to PCPS duration (min) Median (interquartile ranges) RBC transfusion within 24 h SOFA score SAPS II score Lactate (mg/dL) Arterial blood pH Hemoglobin (mg/dL) Sodium (mmol/L) Bilirubin (mg/dL) Creatinine (mg/dL)
All
Survivor
Non-survivor
p-value
40(48.2) 12(14.4) 17(20.5) 14(16.9)
16(47.1) 6(17.6) 7(20.6) 5(14.7)
24(49.0) 6(12.2) 10(20.4) 9(18.4)
38(45.8) 31(37.3) 14(16.9) 75(90.4) 11(13.3) 33(39.8) 39(47.0) 41(49.4) 37.2 ± 26.4 30 (18 – 60)
17(50.0) 11(32.4) 6(17.6) 32(94.1) 0(0) 13(38.2) 21(61.7) 23(67.6) 24.0 ± 17.9 20 (10 – 30)
21(42.9) 20(40.8) 8(16.3) 43(87.8) 11(22.4) 20(40.8) 18(36.7) 18(36.7) 46.4 ± 27.6 46 (23 – 60)
34 (41.0) 66.5 ± 65.4 50 (30–70)
21 (61.8) 69.2 ± 84.6 38 (20–63)
13 (26.5) 64.7 ± 48.5 60 (40–73)
0.002⁎ 0.764 0.082
6.5 ± 9.8 14.1 ± 3.5 76.1 ± 18.5 9.6 ± 5.7 7.16 ± 0.82 9.6 ± 2.5 138.5±17.1 1.7 ± 3.3 1.68 ± 1.20
7.8 ± 12.0 14.7 ± 3.7 77.9 ± 19.1 7.1 ± 4.4 7.30 ± 0.18 9.8 ± 2.7 136.5±24.8 1.2 ± 0.8 1.53 ± 0.90
5.6 ± 7.9 13.7 ± 3.3 74.8 ± 18.2 11.8 ± 5.9 7.07 ± 1.05 9.4 ± 2.4 139.8 ± 8.3 2.1 ± 4.2 1.79 ± 1.37
0.307 0.214 0.456 0.002⁎ 0.210 0.449 0.392 0.227 0.337
0.999 0.537 0.999 0.771 0.655 0.494 0.999 0.462 0.002⁎ 0.999 0.028⁎ 0.008⁎ b0.001⁎ b0.001⁎
Abbreviations: PEA, pulseless electrical activity; VT, ventricular tachycardia; V-fib, ventricular fibrillation; PCPS, extracorporeal life support; RBC, red blood cell; SOFA, Sequential Organ Failure Assessment score; SAPS II, simplified acute physiology score. a Intensive care unit includes coronary care unit and postoperative recovery room. ⁎ p b 0.05 by Fisher's exact test or Mann–Whitney U-test appropriately.
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disease that blocked the insertion of arterial cannulas. The median of PCPS support duration was 42 h, which was not significantly different between the in-hospital survivors and non-survivors. Among the nonsurvivors, 63.2% (31/49) experienced a ROSC. 28.6% (14/49) of the non-survivors were weaned from the PCPS but eventually expired, primarily due to multiple organ failure. Intra-aortic balloon counterpulsation (IABP) was used in 42.2% (35/83) of patients either with the PCPS or after PCPS weaning, when the left ventricular function was severely deteriorated or was not sufficiently recovered. There were no significant differences in the use of IABP between the in-hospital survivors and non-survivors. Revascularization or major cardiac surgery including 7 cases of heart transplantations was performed in 43.4% (36/83) of the patients after PCPS. These procedures were more common in the patients who survived to discharge (58.8%, 20/34) compared to the non-survivors (32.7%, 16/49) (p = 0.025) (Table 3). 3.3. Outcome analysis The survival-to-discharge rate was 41.0% (34/83). Of those who did survive, 85.3% (29/34) had no severe neurological sequalae. Among univariate predictors listed in Table 4, the duration of CPR was the most important factor for survival-to-discharge. Using a receiver operating characteristic (ROC) curve analysis, the best discriminative CPR duration for survival-to-discharge was determined to be 35 min (sensitivity 63.2%, specificity 82.3%, c-statistics = 0.744). We developed a logistic regression model to show the relationship between CPR duration and the probability of survival-to-discharge Table 3 Clinical outcome.
PCPS success PCPS attempt during CPR PCPS duration (h) Median (interquartiles) PCPS weaning success ICU stay (days) Median (interquartiles) IABP Ventilator Renal replacement therapy Complications Limb ischemia PCPS site bleeding Repair of wound Stroke† Significant hemolysis Pulmonary hemorrhage Gastrointestinal bleeding Revascularization PCI CABG Non-coronary cardiac surgery Heart transplantation Any cardiac surgery or revascularization Noncardiac surgery ROSC after PCPS Neurologic recovery CPC 1–2 CPC 3–4 CPC 5
All (n = 83)
Survivor (n = 34)
Non-survivor (n = 49)
p-value
81 (97.6) 53 (63.9) 73.4±110.6 42 (8–91) 48 (57.8) 17.8 ± 21.6 9 (4–21) 35 (42.2) 82 (98.8) 26 (31.3)
34 (100) 17 (50.0) 82.0 ± 138.6 51 (19–93) 34 (100) 22.3 ± 18.7 17 (8–33) 16 (47.1) 34 (100) 6 (17.6)
47 (95.9)a 36 (73.5) 67 ± 87 40 (6–94) 14 (28.6) 14.6 ± 23.1 4 (3–17) 19 (38.8) 48 (98.0) 20 (40.8)
0.510 0.038⁎ 0.561 0.379 b0.001⁎
7 (8.4) 16 (19.3) 3 (3.6) 4 (4.8) 1 (1.2) 4 (4.8) 9 (10.8) 28 (33.7) 21 (25.3) 7 (8.4) 4 (4.8)
2 (5.9) 7 (20.6) 2 (5.9) 2 (5.9) 0 (0) 0 (0) 3 (8.8) 16 (47.1) 11 (32.4) 5 (14.7) 2 (5.9)
5 (10.2) 9 (18.4) 1 (2.0) 2 (4.1) 1 (2.0) 4 (8.2) 6 (12.2) 12 (24.5) 10 (20.4) 2 (4.1) 2 (4.1)
0.695 0.999 0.565 0.999 0.999 0.141 0.731 0.037⁎ 0.305 0.117 0.999
7 (8.4) 36 (43.4)
5 (14.7) 20 (58.8)
2 (4.1) 16 (32.7)
0.117 0.025⁎
7 (8.4) 65 (78.3)
3 (8.8) 34 (100)
4 (8.2) 31 (63.2)
0.999 b0.001⁎
35 (42.2) 7 (8.4) 41 (49.4)
29 (85.3) 5 (14.7) 0 (0)
6 (12.2) 2 (4.1) 41 (83.7)
b0.001⁎ 0.117 b0.001⁎
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Table 4 Predictors for in-hospital death. OR
95% CI
p-value
Univariate analysis Age (year) Age ≥ 67 years VT or V-fib Defibrillation CPR duration (min) CPR time ≥ 35 min ROSC before PCPSa PCPS duration (h) Lactate (mg/dL) Lactate ≥ 9.9 mg/dL SOFA score SAPS II score Renal replacement therapy Coronary revascularization Any cardiac surgery or revascularization Incomplete neurological recoveryb
1.008 3.385 0.359 0.278 1.042 8.037 0.224 0.999 1.194 2.956 0.921 0.991 3.218 0.641 0.339 41.567
0.983–1.034 1.283–8.934 0.146–0.887 0.110–0.700 1.019–1.067 2.796–23.001 0.087–0.571 0.995–1.003 1.057–1.349 1.032–8.467 0.808–1.049 0.967–1.015 1.127–9.195 0.333–1.236 0.137–0.841 11.594–149.030
0.528 0.014⁎ 0.026⁎ 0.007⁎ b0.001⁎ b0.001⁎ 0.002⁎
Multivariate analysis Age ≥ 67 year Defibrillation CPR duration ≥ 35 min ROSC before PCPS Lactate ≥ 9.9 mg/dL Renal replacement therapy Any cardiac surgery or revascularization
3.387 0.163 11.210 0.587 1.691 5.101 2.089
0.890–16.549 0.041–0.648 2.366–53.118 0.144–2.392 0.441–6.492 1.291–20.145 0.501–8.715
0.562 0.004⁎ 0.044⁎ 0.214 0.451 0.029⁎ 0.184 0.020⁎ b0.001⁎
0.071 0.010⁎ 0.002⁎ 0.458 0.444 0.020⁎ 0.312
OR, odds ratio; 95% CI, 95% confidence interval. a ROSC in 41.0% (49 cases). b Defined as CPC ≥ 3. ⁎ P b 0.05 by logistic regression analysis.
[11]. The probability of survival-to-discharge from the hospital decreased approximately 1% for each 1 min of extended CPR. Survival-to-discharge in our study population was approximately 65%, 55%, 45%, 35%, and 26% when the duration of CPR was 10, 20, 30, 40, and 50 min, respectively (Fig. 2). The two additional deaths after discharge should be described here. An 81-year old male was treated with PCPS after emergent
0.112 b0.001⁎ 0.503 0.999 0.031⁎
Abbreviations: IABP, intraaortic balloon counterpulsation; PCI, percutaneous coronary intervention; CABG, coronary artery bypass surgery; ROSC, recovery of spontaneous circulation; CPC, cerebral performance categories. † Stroke: all ischemic except one hemorrhagic stroke in non-survivor. a PCPS was not successfully introduced to two patient with severe peripheral artery disease. ⁎ p b 0.05 by Fisher's exact or Mann–Whitney U-test, appropriately.
Fig. 2. Probability of survival-to-discharge and CPR duration. Probability of survivalto-discharge (solid line) and 95% confidence interval (CI) (dotted line) was calculated according to the model used in logistic regression. logit (CPR duration) = e(1.047 − 0.042 × CPR duration). Probability of survival = logit (CPR duration) / (1 + logit (CPR duration)). Probability of survival-to-discharge = 74% at the point of CPR duration = 0 min was theoretically calculated. Black filled dot shows the point that CPR duration = 35 min, which was the most discriminating point between in-hospital survivors and non-survivors.
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Table 5 Predictors for 6-month death. P
HR
95% CI
p-value
Univariate analysis Age (year) Age ≥ 67 year VT or V-fib Defibrillation CPR duration (min) CPR time ≥ 35 min ROSC before PCPSa PCPS duration (h) Lactate (mg/dL) Lactate ≥ 9.9 mg/dL SOFA score SAPS II score Renal replacement therapy Revascularization Any cardiac surgery or revascularization Incomplete neurological recovery
1.013 2.482 0.432 0.370 1.021 3.309 0.330 0.998 1.111 2.000 0.961 0.996 1.463 0.536 0.422 9.774
0.995–1.031 1.420–4.341 0.243–0.771 0.207–0.661 1.011–1.031 1.855–.902 0.175–0.624 0.995–1.002 1.046–1.179 1.137–3.517 0.891–1.036 0.981–1.010 0.832–2.571 0.280–1.025 0.233–0.766 4.327–22.077
0.158 0.001⁎ 0.004⁎ 0.001⁎ b0.001⁎ b0.001⁎ 0.001⁎
Multivariate analysis Age ≥ 67 year Defibrillation CPR duration ≥ 35 min ROSC before PCPS Lactate ≥ 9.9 mg/dL Any cardiac surgery or revascularization
2.130 0.413 3.129 0.727 0.982 0.754
1.123–4.040 0.224–0.764 1.602–6.112 0.342–1.544 0.537–1.799 0.404–1.408
0.307 0.001⁎ 0.016⁎ 0.302 0.556 0.186 0.060 0.005⁎ b0.001⁎ 0.021⁎ 0.005⁎ 0.001⁎ 0.407 0.954 0.376
HR, hazard ratio; 95% CI, 95% confidence interval. a ROSC in 41.0% (49 cases). ⁎ p b 0.05 by Cox regression analysis.
prosthetic aortic valve replacement surgery. He suffered postcardiotomy cardiac arrest due to severe left ventricular dysfunction accompanied with complete atrioventricular block. He was weaned off the PCPS after 70 h, but his cerebral performance category (CPC) score was poor. He was discharged from the hospital 10 days later and expired on day 14 after the arrest. Another death was a 57-year old male who was treated with 1 h of resuscitation and 9 days of PCPS after coronary artery bypass surgery. He was weaned off the PCPS 54 h later, but his CPC score was very poor. He was discharged from the hospital 24 days later and expired on day 100 after the arrest. Regarding 6-month survival, the duration of CPR was also the most important factor among univariate parameters listed in Table 5, and the best discriminative CPR duration was 35 min. Both the survivalto-discharge rate and 6-month survival rate for patients with a CPR duration b 35 min was significantly higher compared to patients with
a CPR duration ≥ 35 min (60.9% versus 16.2%, p = 0.001 by Fischer's exact test; 58.7% versus 13.5%, p b 0.001 by log-rank test) (Fig. 3). A multivariate logistic regression analysis using significant univariate predictors revealed that independent predictors of in-hospital death were not attempting defibrillation, CPR duration ≥35 min, and renal replacement therapy (Table 4). Not attempting defibrillation, CPR duration ≥35 min, and age ≥ 67 years were independent predictors of death during the 6-month follow-up period according to the Cox's proportional hazard model (Table 5). 4. Discussion In our study population, the survival-to-discharge of cardiac arrest victims who were treated with auto-priming percutaneous cardiopulmonary support device was 41%, and the 6-month survival rate was 39%. Especially, when the duration of CPR was less than 35 min, 6-month survival rate of 60% and absence of severe neurological sequalae of 85.3% in the patients could be achieved, which strongly supports that rapid stabilization of hemodynamic status of arrest victims is critical for survival [10,11]. For over four decades, numerous efforts have been made to improve the survival of in-hospital cardiac arrest victims. Although the survival have improved with the early initiation of bystander CPR and early defibrillation [20,21], the overall survival rate of in-hospital cardiac arrest still remains unsatisfactory [3,4]. In addition, the effectiveness of both immediate defibrillation and CPR decreases rapidly approximately 10 min after the start of cardiac arrest [8,22]. This could be explained by the lack of adequate cerebral and coronary perfusion, as well as the subsequent accumulation of circulating metabolic factors in the context of the 3-phase time-sensitive model of cardiac arrest which was proposed by Weisfeldt and Becker [23,24]. Our study results suggest that the restoration of cerebral and coronary perfusion by mechanical hemodynamic support could improve the chances for survival, elongates the time window of effective CPR, and is a promising treatment modality for the circulatory and metabolic phase of cardiac arrest. In our study, the survival-to-discharge rate for patients who received emergency revascularization or non-coronary cardiac surgery, including heart transplantation, was 55.6%. This is comparable to recent studies which showed an acceptable survival rate of 55% to 67% in postresuscitation revascularization [25–27]. Our study results suggest that acceptable rates of survival could be achieved using mechanical restoration of cerebral and coronary perfusion even in patients who have a mean duration of CPR of 37 min.
Fig. 3. Survival analysis according to the CPR duration. Kaplan–Meier analysis of 6-month survival of cardiac arrest patients treated with CPR and PCPS according to the duration of CPR. p b 0.001 by log rank test.
I.J. Jo et al. / International Journal of Cardiology 151 (2011) 12–17
The severity of organ failure, evaluated by maximum SOFA scores and the SAPS II values, was not different between the survivors and nonsurvivors. In addition, the mortality rate of our study subjects (59%) was far below the estimated mortality using the SAPS II (82.1%) or maximum SOFA scores (N80%). Enhanced tolerance to cardiogenic shock using mechanical hemodynamic support may reduce mortality despite very high SAPS II and SOFA scores. New scoring systems for survival prediction would be warranted for mechanically supported patients who do not respond to conventional CPR [28]. There are several limitations that should be noted here. Our result could not be applied to institutes without experienced PCPS teams [10,15]. Most of all, the result was obtained from retrospective analysis of single center experience. The outcome of CPR supported with PCPS was not compared with CPR alone without PCPS. The in-hospital survival rate of CPR assisted with PCPS was 41.0% (34/83) by average, and was still 19% even when CPR was performed before PCPS for 60 min (Fig. 2). This is still slightly higher than that of conventional CPR without PCPS of same period in our institution, 14.2% (86/604), and also higher than previously published in-hospital CPR results [3,4]. However, given the heterogenous background of in-hospital CPR and the scarcity of conventional CPR performed as long as CPR assisted with PCPS, direct comparison of two resuscitation strategy would be hardly conclusive. The each use of PCPS for CPR victims with various entities such as ischemic cardiac arrest, non-ischemic cardiac arrest, post-cardiotomy, or myocarditis, was not investigated. In addition, randomized trial of resuscitation strategy is very difficult in clinical practice. So our data should be interpreted as suggestive and not conclusive that CPR assisted with PCPS is definitely more effective that conventional CPR, which require further study. The number of patients and 6-month follow-up period may not be sufficient to draw definite conclusions about the long-term outcome. The cause of out-of-hospital death was not investigated. Finally, therapeutic hypothermia, which is recommended in cardiac arrest of cardiac origin, was not applied. The additive or synergistic effect of hypothermia in the setting of higher tissue perfusion with mechanical hemodynamic support would require further study [29]. 5. Conclusion Our study showed that the outcome of CPR assisted with autopriming portable PCPS for in-hospital cardiac arrest patients was acceptable. Our results strongly suggest that PCPS could improve the current outcome of in-hospital cardiac arrest. Acknowledgements This study was supported by grants from the Samsung Medical Center Clinical Research Development Program grant, # CRS-108092 and # CRS-107462, the In-Sung Foundation for Medical Research, and Korea Institute of Medicine, Seoul, Korea. The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology [30]. References [1] Ebell MH, Becker LA, Barry HC, Hagen M. Survival after in-hospital cardiopulmonary resuscitation. A meta-analysis. J Gen Intern Med 1998;13:805–16. [2] Bloom HL, Shukrullah I, Cuellar JR, Lloyd MS, Dudley Jr SC, Zafari AM. Long-term survival after successful inhospital cardiac arrest resuscitation. Am Heart J 2007;153: 831–6. [3] Peberdy MA, Kaye W, Ornato JP, et al. Cardiopulmonary resuscitation of adults in the hospital: a report of 14720 cardiac arrests from the National Registry of Cardiopulmonary Resuscitation. Resuscitation 2003;58:297–308.
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A consensus statement from the International Liaison Committee on Resuscitation (American Heart Association, Australian and New Zealand Council on Resuscitation, European Resuscitation Council, Heart and Stroke Foundation of Canada, InterAmerican Heart Foundation, Resuscitation Council of Asia, and the Resuscitation Council of Southern Africa); the American Heart Association Emergency Cardiovascular Care Committee; the Council on Cardiovascular Surgery and Anesthesia; the Council on Cardiopulmonary, Perioperative, and Critical Care; the Council on Clinical Cardiology; and the Stroke Council. Circulation 2008;118:2452–83. [8] Hajbaghery MA, Mousavi G, Akbari H. Factors influencing survival after in-hospital cardiopulmonary resuscitation. Resuscitation 2005;66:317–21. [9] Nichol G, Karmy-Jones R, Salerno C, Cantore L, Becker L. Systematic review of percutaneous cardiopulmonary bypass for cardiac arrest or cardiogenic shock states. Resuscitation 2006;70:381–94. 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Improved survival after cardiac arrest using emergent autopriming percutaneous cardiopulmonary support. Ann Thorac Surg 2006;82:651–6. [16] Cummins RO, Chamberlain D, Hazinski MF, et al. Recommended guidelines for reviewing, reporting, and conducting research on in-hospital resuscitation: the inhospital ‘Utstein style’. American Heart Association. Circulation 1997;95:2213–39. [17] Le Gall JR, Lemeshow S, Saulnier F. A new Simplified Acute Physiology Score (SAPS II) based on a European/North American multicenter study. Jama 1993;270:2957–63. [18] Ferreira FL, Bota DP, Bross A, Melot C, Vincent JL. Serial evaluation of the SOFA score to predict outcome in critically ill patients. Jama 2001;286:1754–8. [19] Prohl J, Rother J, Kluge S, et al. Prediction of short-term and long-term outcomes after cardiac arrest: a prospective multivariate approach combining biochemical, clinical, electrophysiological, and neuropsychological investigations. Crit Care Med 2007;35:1230–7. 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Six-month outcome of emergency percutaneous coronary intervention in resuscitated patients after cardiac arrest complicating ST-elevation myocardial infarction. Circulation 2007;115:1354–62. [26] Gorjup V, Radsel P, Kocjancic ST, Erzen D, Noc M. Acute ST-elevation myocardial infarction after successful cardiopulmonary resuscitation. Resuscitation 2007;72: 379–85. [27] Hosmane VR, Mustafa NG, Reddy VK, et al. Survival and neurologic recovery in patients with ST-segment elevation myocardial infarction resuscitated from cardiac arrest. J Am Coll Cardiol 2009;53:409–15. [28] Massetti M, Tasle M, Le Page O, et al. Back from irreversibility: extracorporeal life support for prolonged cardiac arrest. Ann Thorac Surg 2005;79:178–83 (discussion 183-4). [29] Nagao K, Hayashi N, Kanmatsuse K, et al. Cardiopulmonary cerebral resuscitation using emergency cardiopulmonary bypass, coronary reperfusion therapy and mild hypothermia in patients with cardiac arrest outside the hospital. 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Contents lists available at ScienceDirect
International Journal of Cardiology j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / i j c a r d
Outcome of in-hospital adult cardiopulmonary resuscitation assisted with portable auto-priming percutaneous cardiopulmonary support Ik Joon Jo a,1, Tae Gun Shin a,1, Min Sub Sim a, Hyoung Gon Song a, Yeon Kwon Jeong a, Yong-Bien Song b, Joo-Yong Hahn b, Seung Hyuk Choi b, Hyeon-Cheol Gwon b, Eun-Seok Jeon b, Wook Sung Kim c, Young Tak Lee c, Kiick Sung c,⁎, Jin-Ho Choi a,b,⁎ a b c
Departments of Emergency Medicine, Cardiac and Vascular Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea Medicine, Cardiac and Vascular Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea Thoracic Surgery, Cardiac and Vascular Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
a r t i c l e
i n f o
Article history: Received 9 July 2009 Received in revised form 17 November 2009 Accepted 17 April 2010 Available online 15 May 2010 Keywords: Percutaneous cardiopulmonary support Cardiopulmonary resuscitation Percutaneous cardiopulmonary support Cardiopulmonary resuscitation In-hospital cardiac arrest
a b s t r a c t Background: Outcome from in-hospital cardiopulmonary resuscitation (CPR) is still unsatisfactory. CPR assisted with percutaneous cardiopulmonary support (PCPS) is expected to improve the outcome of inhospital CPR. Methods: We retrospectively analyzed 83 consecutive cases of adult in-hospital CPR assisted by a portable pre-assembled auto-priming PCPS system (EBS, Terumo, Japan) from January 2004 to December 2007. Results: PCPS was successfully performed in 97.6% of the patients and could be weaned in 57.8% of the patients. The survival-to-discharge rate was 41.0% with an acceptable neurological status in 85.3% of the patients. The 6-month survival was 38.6%. Survival-to-discharge decreased about 1% for each 1 min increase in the duration of CPR. The probability of survival was about 65%, 45%, and 19% when the duration of CPR was 10, 30, or 60 min, respectively. Multivariate analysis adjusted with clinical factors including organ dysfunction severity scores revealed that defibrillation and CPR duration less than 35 min were independent predictors for both survival-to-discharge (odds ratio = 8.0, 95% CI = 2.8–23.0, p b 0.001) and 6-month survival (hazard ratio = 3.3, 95% CI = 1.9–5.9, p b 0.001). Conclusions: Our results showed that CPR assisted with PCPS results in an acceptable survival-to-discharge rate and mid-term prognosis. © 2010 Elsevier Ireland Ltd. All rights reserved.
1. Introduction The overall survival rate of patients who experience in-hospital cardiac arrest remains unsatisfactory [1,2]. For example, large-scale nationwide registries conducted in United States and Taiwan showed that the survival rate of patients who required in-hospital CPR was 17 to 18% despite a median defibrillation time of less than 1 min [3,4]. Even when the resumption of spontaneous circulation (ROSC) is achieved after CPR, the survival-to-discharge rate is only 29 to 33% and has not changed significantly in the past half-century [5–7]. One of the greatest limitations of CPR is the very narrow time window of
⁎ Corresponding authors. Choi is to be contacted Department of Emergency Medicine, Department of Medicine, Chest Pain Center, Cardiac and Vascular Center, Samsung Medical Center, 50 Irwon-dong, Gangnam-ku, Seoul, 135-710, Republic of Korea. Tel.: +82 2 3410 3419; fax: +82 2 3410 3849. Sung, Department of Thoracic Surgery, Cardiac and Vascular Center, Samsung Medical Center. 50 Irwon-dong, Gangnam-ku, Seoul, 135-710, Republic of Korea. Tel.: +82 2 3410 6849; fax: +82 2 3410 6541. E-mail addresses: [email protected] (K. Sung), [email protected] (J.-H. Choi). 1 Both authors equally contributed to this work. 0167-5273/$ – see front matter © 2010 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijcard.2010.04.050
effectiveness. Most studies showed that a CPR duration of more than 20 min has resulted in a survival rate of less than 5% [3,4,8]. Mechanical support of the cardiopulmonary system has been attempted to improve the result of CPR [9]. Extracorporeal membrane oxygenation (ECMO), which is composed of a centrifugal pump and a membranous artificial lung which provide hemodynamic support, has shown promising outcomes in recent clinical investigations [10–12]. The percutaneous cardiopulmonary support (PCPS) is a portable preassembled heparin-coated ECMO system that can be primed immediately and applied percutaneously in emergency situations [13,14]. We have used PCPS as an adjunct to conventional CPR and post-resuscitation care since 2004 [15]. We investigated the outcomes and mid-term survival of patients who suffered in-hospital cardiac arrest and were treated by CPR assisted with PCPS. 2. Methods 2.1. Study subjects Between January 2004 and December 2007, 164 cases of emergency PCPS have been performed on patients with intractable cardiogenic shock without cardiac arrest or cardiac arrest at Samsung Medical Center, a 1900-bed tertiary academic hospital in urban area.
I.J. Jo et al. / International Journal of Cardiology 151 (2011) 12–17 Patients on PCPS for hemodynamic support without CPR and those who previously received it before CPR were excluded (n=62). Pediatric patients, who were younger than 15 years, also excluded (n=19). After accounting for these exclusions, we retrospectively reviewed the medical records of 83 adult patients who suffered a cardiac arrest, and received PCPS during CPR or within at least 6 h immediately after ROSC. The institutional review board of the Samsung Medical Center approved the study protocol. A CPR event was defined as the loss of a palpable or monitored pulse and the loss of respiration despite aggressive medical therapy which required the application of chest compressions. The CPR duration was defined as the interval between the initiation of CPR and the initiation of PCPS when it was performed before successful ROSC, or the duration of chest compressions when it was used after ROSC [11]. ROSC was defined as the return of a spontaneous heartbeat with a detectable peripheral arterial pulsation. Because patients with PCPS were frequently dependent on artificial circulation, ROSC was confirmed after brief reduction of PCPS flow. 2.2. CPR and ECMO teams The CPR team consists of emergency physicians certified in advanced cardiac lifesupport, as well as nurses and paramedics. They responded to most cases of in-hospital cardiac arrest, except cases in the intensive care unit which were treated by intensivists. The PCPS team consists of experienced interventional cardiologists, cardiovascular surgeons, and paramedics. CPR team leader called the PCPS team in the following conditions; when there was no ROSC after 10 min of CPR, when ROSC could not be maintained for more than 20 min, or when the patient could not be expected to recover due to underlying severe left ventricular dysfunction or coronary artery disease despite short CPR duration less than 10 min. During the postresuscitation period after ROSC, the
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PCPS team was also called when cardiogenic shock was unresponsive to conventional measures, or when ventricular arrhythmia was refractory. In cases of patients with previously known severe irreversible brain damage, terminal malignancy, trauma with uncontrolled bleeding, and those who previously signed ‘do not attempt resuscitation’, the decisions for PCPS application were deterred. Verbal permission for the initiation of the PCPS was obtained from the relatives. Written informed consent was obtained later. Both CPR and PCPS teams were available at all times. PCPS was usually available within 10 min during the day. During night shifts or weekend, it was available within 10 to 20 min.
2.3. Procedures The Capiox Emergency Bypass System (EBS)™ (Terumo, Tokyo, Japan) was used in all cases (Fig. 1). The system consists of a portable extracorporeal life-support controller with internal back-up battery and a disposable bypass circuit integrated with a heparin-coated membrane oxygenator and centrifugal pump. Trained personnel are able to move the device to the bedside, connect saline fluid and oxygen lines, and start the device immediately. The system completed de-airing priming process automatically within 5 min. Device insertion was performed by attending interventional cardiologists or cardiovascular surgeons who were house staffs on duty. Physicians in their learning curve could perform the procedure under direct guidance of staffs after assistance for 6 months. Vascular cannulation was mostly done percutaneously using the Seldinger technique. Surgical exposure was performed in difficult cases, such as patients with peripheral artery disease or severe obesity. Vascular cannula size was 14 to 21 French for artery, and 21 to 28 French for vein. A catheter was inserted into the femoral artery to facilitate distal limb perfusion in the event of leg ischemia after arterial cannulation.
Fig. 1. A percutaneous cardiopulmonary support (PCPS), Terumo EBS. Panel A: A PCPS controller and accessories built in mobile cart. If necessary, the desktop computer-sized controller and other parts can be detached and carried by hands. Panel B: A disposable PCPS circuit with integrated pump and heparin-coated oxygenator, which was partially opened from aseptic package. Panel C: Scheme of PCPS support. A venous cannula located in right atrium and intravenous cava drains hypoxic venous blood. The blood is sent to arterial cannula by centrifugal pump after gas exchange at oxygenator.
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Anticoagulation was accomplished by a bolus injection of unfractionated heparin, which was followed by a continuous intravenous infusion of heparin to maintain the activated clotting time between 180 and 200 s. The flow rate was set above 2.2 L/min/body surface area (m2) initially, and was adjusted subsequently to maintain a mean arterial pressure above 65 mmHg. The partial pressure of arterial oxygen in the right arm was maintained at greater than 100 mmHg to ensure the sufficient oxygenation of the brain. Transfusion of red blood cell and fresh frozen plasma was performed to maintain intravascular volume which was essential to functional PCPS circuit, and to maintain hematocrit which was important to tissue oxygen delivery. Usually 5 to 7 units of red blood cell and 3 to 5 units of fresh frozen plasma were required within first 24 h. Detailed management was previously reported by us [15]. Daily echocardiograms were performed to evaluate the recovery of left ventricular function and to determine the potential for developing an intraventricular thrombus. Minimal dose of intravenous catecholamine was used to maintain a pulsatile arterial waveform and avoid the development of a left ventricular thrombus. Weaning off of the PCPS was considered when the patient was hemodynamically stable and adequately oxygenated under a low dose of intravenous catecholamines (dopamine or dobutamine of less than 5 μg/kg/min) and a PCPS flow of less than 1 L/min for more than 4 h. The PCPS circuit was removed when the patient was stable for more than 20 min with a PCPS flow rate of 0.5 L/min. If the femoral artery was atherosclerotic or a cannula larger than 21 French was used, the femoral arteriotomy site was surgically repaired. Otherwise, hemostasis could be achieved by prolonged manual compression. The femoral vein was closed using a simple percutaneous suture and manual compression. If the weaning was unsuccessful in 3 to 4 days, the disposable bypass circuit was replaced with a new circuit at the bedside, and a ventricular assist device or heart transplantation was considered in the absence of contraindications. The termination of PCPS was considered with the consent of the family of the patient when there was intractable multi-organ failure or severe neurologic damage consistent with a vegetative state or brain death. 2.4. Data collection and statistical analysis Clinical data was collected according to the modified guidelines for reviewing and reporting in-hospital resuscitations [16]. The severity of organ dysfunction was measured using the Simplified Acute Physiology Score (SAPS) II at the time of the arrest, and the maximum value of the Sequential Organ Failure Assessment (SOFA) during admission [17,18]. The neurological status of each patient at the time of discharge was assessed using the Glasgow–Pittsburgh cerebral-performance categories (CPC) score [19]. The primary endpoint was survival-to-discharge. Continuous variables were expressed as the mean± standard deviation or median with interquartile ranges, if necessary. Continuous and categorical variables were compared using Mann–Whitney U test or Fisher's exact test, respectively. A multivariate logistic regression model using forward conditional method was used to seek independent predictors of survival. The probability of survival according to the duration of CPR, which has been known to be one of most significant prognostic factors [8], was calculated according to the method of Chen [11]. Kaplan–Meier curve was plotted to show the trend of mid-term survival. SPSS version 13.0 (SPSS Inc., Chicago IL, USA) was used for the statistical analysis. A two-tailed P b 0.05 was considered statistically significant.
3. Results 3.1. CPR-related parameters The most common cause of cardiac arrest in this study was acute coronary syndrome (48.2%). The demographics and pre-existing comorbidities were similar between the in-hospital survivors (41.0%, N = 34) and non-survivors (59.0%, N = 49). Defibrillation was attempted in all patients who suffered from a ventricular tachyarrhythmia and two patients who had an undetermined rhythm (Table 1). The location or time zone of CPR was also not different between the inhospital survivors and non-survivors. CPR duration was shorter for the inhospital survivors compared to the non-survivors (24.0±17.9 min versus 46.4±27.6 min, pb 0.001). ROSC before a PCPS attempt was more common for the in-hospital survivors compared to the non-survivors (61.8% versus 26.5%, p=0.002). Organ dysfunction parameters in the first 24 h were not significantly different between the in-hospital survivors and non-survivors. However, lactate level was significantly lower in the in-hospital survivors compared to the non-survivors (7.1±4.4 mg/dL versus 11.8±5.9 mg/dL, p=0.002) (Table 2). 3.2. PCPS and in-hospital care parameters PCPS introduction was successful in 97.6% (81/83) of the patients. The two patients in whom it failed had severe peripheral artery
Table 1 Pre-CPR parameters.
N Age, mean ± SD Median (interquartile ranges) Male gender Pre-existing comorbidity Diabetes Hypertension Stroke Chronic renal failure Malignancy Lung insufficiency GI bleeding Causes of arrest Acute coronary syndrome Aggravation of heart failure Myocarditis Pulmonary thromboembolism Other circulatory obstructiona Primary arrhythmia Unknown Clinical situation Post any invasive procedure Post cardiac surgery Post noncardiac surgery Post cardiac catheterization
All
Survivor
Non-survivor p-value
83 (100) 58.1 ± 17.3 63 (48–70) 53 (63.9)
34 (41.0) 56.7 ± 16.3 62 (48–67) 21 (61.8)
49 (59.0) 59.1 ± 18.1 67 (50–71) 32 (65.3)
– 0.538 0.238 0.8
18 (21.7) 29 (34.9) 5 (6.0) 7 (8.4) 8 (9.6) 5 (6.0) 9 (10.8)
8 (20.0) 11 (32.4) 3 (8.8) 2 (5.9) 2 (5.9) 2 (5.9) 3 (8.8)
10 (23.3) 18 (36.7) 2 (4.1) 5 (10.2) 6 (12.2) 3 (6.1) 6 (12.2)
0.790 0.816 0.396 0.999 0.462 0.999 0.731
40 (48.2) 16 (19.3) 2 (2.4) 4 (4.8)
17 (50.0) 6 (17.6) 1 (2.9) 2 (5.9)
23 (46.9) 10 (20.4) 1 (2.0) 2 (4.1)
0.826 0.999 0.999 0.999
5 (6.0)
4 (11.8)
1 (2.0)
0.153
1 (1.2) 15 (18.1)
1 (2.9) 4 (11.8)
0 (0) 11 (22.4)
0.410 0.257
47 14 16 17
20 (58.8) 8 (23.5) 5 (14.7) 7 (20.6)
27 (55.1) 6 (12.2) 11 (22.4) 10 (20.4)
0.823 0.236 0.414 0.999
(56.6) (16.9) (19.3) (20.5)
Data shown as number (percent) or mean ± SD. p-value by Fisher's exact test or Mann– Whitney U-test, appropriately. a Pericardial tamponade and critical aortic stenosis. Primary arrhythmia includes one case of hypertrophic cardiomyopathy with ventricular fibrillation.
Table 2 CPR and post-CPR parameters.
CPR location Intensive care unita Catheterization lab Emergency room General ward CPR time zone 7 AM–5 PM 5 PM–11 PM 11 PM–7 AM Pre-arrest rhythm monitoring Asystole PEA VT or V-fib Defibrillation CPR duration (min) Median (interquartile ranges) ROSC before PCPS CPR to PCPS duration (min) Median (interquartile ranges) RBC transfusion within 24 h SOFA score SAPS II score Lactate (mg/dL) Arterial blood pH Hemoglobin (mg/dL) Sodium (mmol/L) Bilirubin (mg/dL) Creatinine (mg/dL)
All
Survivor
Non-survivor
p-value
40(48.2) 12(14.4) 17(20.5) 14(16.9)
16(47.1) 6(17.6) 7(20.6) 5(14.7)
24(49.0) 6(12.2) 10(20.4) 9(18.4)
38(45.8) 31(37.3) 14(16.9) 75(90.4) 11(13.3) 33(39.8) 39(47.0) 41(49.4) 37.2 ± 26.4 30 (18 – 60)
17(50.0) 11(32.4) 6(17.6) 32(94.1) 0(0) 13(38.2) 21(61.7) 23(67.6) 24.0 ± 17.9 20 (10 – 30)
21(42.9) 20(40.8) 8(16.3) 43(87.8) 11(22.4) 20(40.8) 18(36.7) 18(36.7) 46.4 ± 27.6 46 (23 – 60)
34 (41.0) 66.5 ± 65.4 50 (30–70)
21 (61.8) 69.2 ± 84.6 38 (20–63)
13 (26.5) 64.7 ± 48.5 60 (40–73)
0.002⁎ 0.764 0.082
6.5 ± 9.8 14.1 ± 3.5 76.1 ± 18.5 9.6 ± 5.7 7.16 ± 0.82 9.6 ± 2.5 138.5±17.1 1.7 ± 3.3 1.68 ± 1.20
7.8 ± 12.0 14.7 ± 3.7 77.9 ± 19.1 7.1 ± 4.4 7.30 ± 0.18 9.8 ± 2.7 136.5±24.8 1.2 ± 0.8 1.53 ± 0.90
5.6 ± 7.9 13.7 ± 3.3 74.8 ± 18.2 11.8 ± 5.9 7.07 ± 1.05 9.4 ± 2.4 139.8 ± 8.3 2.1 ± 4.2 1.79 ± 1.37
0.307 0.214 0.456 0.002⁎ 0.210 0.449 0.392 0.227 0.337
0.999 0.537 0.999 0.771 0.655 0.494 0.999 0.462 0.002⁎ 0.999 0.028⁎ 0.008⁎ b0.001⁎ b0.001⁎
Abbreviations: PEA, pulseless electrical activity; VT, ventricular tachycardia; V-fib, ventricular fibrillation; PCPS, extracorporeal life support; RBC, red blood cell; SOFA, Sequential Organ Failure Assessment score; SAPS II, simplified acute physiology score. a Intensive care unit includes coronary care unit and postoperative recovery room. ⁎ p b 0.05 by Fisher's exact test or Mann–Whitney U-test appropriately.
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disease that blocked the insertion of arterial cannulas. The median of PCPS support duration was 42 h, which was not significantly different between the in-hospital survivors and non-survivors. Among the nonsurvivors, 63.2% (31/49) experienced a ROSC. 28.6% (14/49) of the non-survivors were weaned from the PCPS but eventually expired, primarily due to multiple organ failure. Intra-aortic balloon counterpulsation (IABP) was used in 42.2% (35/83) of patients either with the PCPS or after PCPS weaning, when the left ventricular function was severely deteriorated or was not sufficiently recovered. There were no significant differences in the use of IABP between the in-hospital survivors and non-survivors. Revascularization or major cardiac surgery including 7 cases of heart transplantations was performed in 43.4% (36/83) of the patients after PCPS. These procedures were more common in the patients who survived to discharge (58.8%, 20/34) compared to the non-survivors (32.7%, 16/49) (p = 0.025) (Table 3). 3.3. Outcome analysis The survival-to-discharge rate was 41.0% (34/83). Of those who did survive, 85.3% (29/34) had no severe neurological sequalae. Among univariate predictors listed in Table 4, the duration of CPR was the most important factor for survival-to-discharge. Using a receiver operating characteristic (ROC) curve analysis, the best discriminative CPR duration for survival-to-discharge was determined to be 35 min (sensitivity 63.2%, specificity 82.3%, c-statistics = 0.744). We developed a logistic regression model to show the relationship between CPR duration and the probability of survival-to-discharge Table 3 Clinical outcome.
PCPS success PCPS attempt during CPR PCPS duration (h) Median (interquartiles) PCPS weaning success ICU stay (days) Median (interquartiles) IABP Ventilator Renal replacement therapy Complications Limb ischemia PCPS site bleeding Repair of wound Stroke† Significant hemolysis Pulmonary hemorrhage Gastrointestinal bleeding Revascularization PCI CABG Non-coronary cardiac surgery Heart transplantation Any cardiac surgery or revascularization Noncardiac surgery ROSC after PCPS Neurologic recovery CPC 1–2 CPC 3–4 CPC 5
All (n = 83)
Survivor (n = 34)
Non-survivor (n = 49)
p-value
81 (97.6) 53 (63.9) 73.4±110.6 42 (8–91) 48 (57.8) 17.8 ± 21.6 9 (4–21) 35 (42.2) 82 (98.8) 26 (31.3)
34 (100) 17 (50.0) 82.0 ± 138.6 51 (19–93) 34 (100) 22.3 ± 18.7 17 (8–33) 16 (47.1) 34 (100) 6 (17.6)
47 (95.9)a 36 (73.5) 67 ± 87 40 (6–94) 14 (28.6) 14.6 ± 23.1 4 (3–17) 19 (38.8) 48 (98.0) 20 (40.8)
0.510 0.038⁎ 0.561 0.379 b0.001⁎
7 (8.4) 16 (19.3) 3 (3.6) 4 (4.8) 1 (1.2) 4 (4.8) 9 (10.8) 28 (33.7) 21 (25.3) 7 (8.4) 4 (4.8)
2 (5.9) 7 (20.6) 2 (5.9) 2 (5.9) 0 (0) 0 (0) 3 (8.8) 16 (47.1) 11 (32.4) 5 (14.7) 2 (5.9)
5 (10.2) 9 (18.4) 1 (2.0) 2 (4.1) 1 (2.0) 4 (8.2) 6 (12.2) 12 (24.5) 10 (20.4) 2 (4.1) 2 (4.1)
0.695 0.999 0.565 0.999 0.999 0.141 0.731 0.037⁎ 0.305 0.117 0.999
7 (8.4) 36 (43.4)
5 (14.7) 20 (58.8)
2 (4.1) 16 (32.7)
0.117 0.025⁎
7 (8.4) 65 (78.3)
3 (8.8) 34 (100)
4 (8.2) 31 (63.2)
0.999 b0.001⁎
35 (42.2) 7 (8.4) 41 (49.4)
29 (85.3) 5 (14.7) 0 (0)
6 (12.2) 2 (4.1) 41 (83.7)
b0.001⁎ 0.117 b0.001⁎
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Table 4 Predictors for in-hospital death. OR
95% CI
p-value
Univariate analysis Age (year) Age ≥ 67 years VT or V-fib Defibrillation CPR duration (min) CPR time ≥ 35 min ROSC before PCPSa PCPS duration (h) Lactate (mg/dL) Lactate ≥ 9.9 mg/dL SOFA score SAPS II score Renal replacement therapy Coronary revascularization Any cardiac surgery or revascularization Incomplete neurological recoveryb
1.008 3.385 0.359 0.278 1.042 8.037 0.224 0.999 1.194 2.956 0.921 0.991 3.218 0.641 0.339 41.567
0.983–1.034 1.283–8.934 0.146–0.887 0.110–0.700 1.019–1.067 2.796–23.001 0.087–0.571 0.995–1.003 1.057–1.349 1.032–8.467 0.808–1.049 0.967–1.015 1.127–9.195 0.333–1.236 0.137–0.841 11.594–149.030
0.528 0.014⁎ 0.026⁎ 0.007⁎ b0.001⁎ b0.001⁎ 0.002⁎
Multivariate analysis Age ≥ 67 year Defibrillation CPR duration ≥ 35 min ROSC before PCPS Lactate ≥ 9.9 mg/dL Renal replacement therapy Any cardiac surgery or revascularization
3.387 0.163 11.210 0.587 1.691 5.101 2.089
0.890–16.549 0.041–0.648 2.366–53.118 0.144–2.392 0.441–6.492 1.291–20.145 0.501–8.715
0.562 0.004⁎ 0.044⁎ 0.214 0.451 0.029⁎ 0.184 0.020⁎ b0.001⁎
0.071 0.010⁎ 0.002⁎ 0.458 0.444 0.020⁎ 0.312
OR, odds ratio; 95% CI, 95% confidence interval. a ROSC in 41.0% (49 cases). b Defined as CPC ≥ 3. ⁎ P b 0.05 by logistic regression analysis.
[11]. The probability of survival-to-discharge from the hospital decreased approximately 1% for each 1 min of extended CPR. Survival-to-discharge in our study population was approximately 65%, 55%, 45%, 35%, and 26% when the duration of CPR was 10, 20, 30, 40, and 50 min, respectively (Fig. 2). The two additional deaths after discharge should be described here. An 81-year old male was treated with PCPS after emergent
0.112 b0.001⁎ 0.503 0.999 0.031⁎
Abbreviations: IABP, intraaortic balloon counterpulsation; PCI, percutaneous coronary intervention; CABG, coronary artery bypass surgery; ROSC, recovery of spontaneous circulation; CPC, cerebral performance categories. † Stroke: all ischemic except one hemorrhagic stroke in non-survivor. a PCPS was not successfully introduced to two patient with severe peripheral artery disease. ⁎ p b 0.05 by Fisher's exact or Mann–Whitney U-test, appropriately.
Fig. 2. Probability of survival-to-discharge and CPR duration. Probability of survivalto-discharge (solid line) and 95% confidence interval (CI) (dotted line) was calculated according to the model used in logistic regression. logit (CPR duration) = e(1.047 − 0.042 × CPR duration). Probability of survival = logit (CPR duration) / (1 + logit (CPR duration)). Probability of survival-to-discharge = 74% at the point of CPR duration = 0 min was theoretically calculated. Black filled dot shows the point that CPR duration = 35 min, which was the most discriminating point between in-hospital survivors and non-survivors.
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Table 5 Predictors for 6-month death. P
HR
95% CI
p-value
Univariate analysis Age (year) Age ≥ 67 year VT or V-fib Defibrillation CPR duration (min) CPR time ≥ 35 min ROSC before PCPSa PCPS duration (h) Lactate (mg/dL) Lactate ≥ 9.9 mg/dL SOFA score SAPS II score Renal replacement therapy Revascularization Any cardiac surgery or revascularization Incomplete neurological recovery
1.013 2.482 0.432 0.370 1.021 3.309 0.330 0.998 1.111 2.000 0.961 0.996 1.463 0.536 0.422 9.774
0.995–1.031 1.420–4.341 0.243–0.771 0.207–0.661 1.011–1.031 1.855–.902 0.175–0.624 0.995–1.002 1.046–1.179 1.137–3.517 0.891–1.036 0.981–1.010 0.832–2.571 0.280–1.025 0.233–0.766 4.327–22.077
0.158 0.001⁎ 0.004⁎ 0.001⁎ b0.001⁎ b0.001⁎ 0.001⁎
Multivariate analysis Age ≥ 67 year Defibrillation CPR duration ≥ 35 min ROSC before PCPS Lactate ≥ 9.9 mg/dL Any cardiac surgery or revascularization
2.130 0.413 3.129 0.727 0.982 0.754
1.123–4.040 0.224–0.764 1.602–6.112 0.342–1.544 0.537–1.799 0.404–1.408
0.307 0.001⁎ 0.016⁎ 0.302 0.556 0.186 0.060 0.005⁎ b0.001⁎ 0.021⁎ 0.005⁎ 0.001⁎ 0.407 0.954 0.376
HR, hazard ratio; 95% CI, 95% confidence interval. a ROSC in 41.0% (49 cases). ⁎ p b 0.05 by Cox regression analysis.
prosthetic aortic valve replacement surgery. He suffered postcardiotomy cardiac arrest due to severe left ventricular dysfunction accompanied with complete atrioventricular block. He was weaned off the PCPS after 70 h, but his cerebral performance category (CPC) score was poor. He was discharged from the hospital 10 days later and expired on day 14 after the arrest. Another death was a 57-year old male who was treated with 1 h of resuscitation and 9 days of PCPS after coronary artery bypass surgery. He was weaned off the PCPS 54 h later, but his CPC score was very poor. He was discharged from the hospital 24 days later and expired on day 100 after the arrest. Regarding 6-month survival, the duration of CPR was also the most important factor among univariate parameters listed in Table 5, and the best discriminative CPR duration was 35 min. Both the survivalto-discharge rate and 6-month survival rate for patients with a CPR duration b 35 min was significantly higher compared to patients with
a CPR duration ≥ 35 min (60.9% versus 16.2%, p = 0.001 by Fischer's exact test; 58.7% versus 13.5%, p b 0.001 by log-rank test) (Fig. 3). A multivariate logistic regression analysis using significant univariate predictors revealed that independent predictors of in-hospital death were not attempting defibrillation, CPR duration ≥35 min, and renal replacement therapy (Table 4). Not attempting defibrillation, CPR duration ≥35 min, and age ≥ 67 years were independent predictors of death during the 6-month follow-up period according to the Cox's proportional hazard model (Table 5). 4. Discussion In our study population, the survival-to-discharge of cardiac arrest victims who were treated with auto-priming percutaneous cardiopulmonary support device was 41%, and the 6-month survival rate was 39%. Especially, when the duration of CPR was less than 35 min, 6-month survival rate of 60% and absence of severe neurological sequalae of 85.3% in the patients could be achieved, which strongly supports that rapid stabilization of hemodynamic status of arrest victims is critical for survival [10,11]. For over four decades, numerous efforts have been made to improve the survival of in-hospital cardiac arrest victims. Although the survival have improved with the early initiation of bystander CPR and early defibrillation [20,21], the overall survival rate of in-hospital cardiac arrest still remains unsatisfactory [3,4]. In addition, the effectiveness of both immediate defibrillation and CPR decreases rapidly approximately 10 min after the start of cardiac arrest [8,22]. This could be explained by the lack of adequate cerebral and coronary perfusion, as well as the subsequent accumulation of circulating metabolic factors in the context of the 3-phase time-sensitive model of cardiac arrest which was proposed by Weisfeldt and Becker [23,24]. Our study results suggest that the restoration of cerebral and coronary perfusion by mechanical hemodynamic support could improve the chances for survival, elongates the time window of effective CPR, and is a promising treatment modality for the circulatory and metabolic phase of cardiac arrest. In our study, the survival-to-discharge rate for patients who received emergency revascularization or non-coronary cardiac surgery, including heart transplantation, was 55.6%. This is comparable to recent studies which showed an acceptable survival rate of 55% to 67% in postresuscitation revascularization [25–27]. Our study results suggest that acceptable rates of survival could be achieved using mechanical restoration of cerebral and coronary perfusion even in patients who have a mean duration of CPR of 37 min.
Fig. 3. Survival analysis according to the CPR duration. Kaplan–Meier analysis of 6-month survival of cardiac arrest patients treated with CPR and PCPS according to the duration of CPR. p b 0.001 by log rank test.
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The severity of organ failure, evaluated by maximum SOFA scores and the SAPS II values, was not different between the survivors and nonsurvivors. In addition, the mortality rate of our study subjects (59%) was far below the estimated mortality using the SAPS II (82.1%) or maximum SOFA scores (N80%). Enhanced tolerance to cardiogenic shock using mechanical hemodynamic support may reduce mortality despite very high SAPS II and SOFA scores. New scoring systems for survival prediction would be warranted for mechanically supported patients who do not respond to conventional CPR [28]. There are several limitations that should be noted here. Our result could not be applied to institutes without experienced PCPS teams [10,15]. Most of all, the result was obtained from retrospective analysis of single center experience. The outcome of CPR supported with PCPS was not compared with CPR alone without PCPS. The in-hospital survival rate of CPR assisted with PCPS was 41.0% (34/83) by average, and was still 19% even when CPR was performed before PCPS for 60 min (Fig. 2). This is still slightly higher than that of conventional CPR without PCPS of same period in our institution, 14.2% (86/604), and also higher than previously published in-hospital CPR results [3,4]. However, given the heterogenous background of in-hospital CPR and the scarcity of conventional CPR performed as long as CPR assisted with PCPS, direct comparison of two resuscitation strategy would be hardly conclusive. The each use of PCPS for CPR victims with various entities such as ischemic cardiac arrest, non-ischemic cardiac arrest, post-cardiotomy, or myocarditis, was not investigated. In addition, randomized trial of resuscitation strategy is very difficult in clinical practice. So our data should be interpreted as suggestive and not conclusive that CPR assisted with PCPS is definitely more effective that conventional CPR, which require further study. The number of patients and 6-month follow-up period may not be sufficient to draw definite conclusions about the long-term outcome. The cause of out-of-hospital death was not investigated. Finally, therapeutic hypothermia, which is recommended in cardiac arrest of cardiac origin, was not applied. The additive or synergistic effect of hypothermia in the setting of higher tissue perfusion with mechanical hemodynamic support would require further study [29]. 5. Conclusion Our study showed that the outcome of CPR assisted with autopriming portable PCPS for in-hospital cardiac arrest patients was acceptable. Our results strongly suggest that PCPS could improve the current outcome of in-hospital cardiac arrest. Acknowledgements This study was supported by grants from the Samsung Medical Center Clinical Research Development Program grant, # CRS-108092 and # CRS-107462, the In-Sung Foundation for Medical Research, and Korea Institute of Medicine, Seoul, Korea. The authors of this manuscript have certified that they comply with the Principles of Ethical Publishing in the International Journal of Cardiology [30]. References [1] Ebell MH, Becker LA, Barry HC, Hagen M. Survival after in-hospital cardiopulmonary resuscitation. A meta-analysis. J Gen Intern Med 1998;13:805–16. [2] Bloom HL, Shukrullah I, Cuellar JR, Lloyd MS, Dudley Jr SC, Zafari AM. Long-term survival after successful inhospital cardiac arrest resuscitation. Am Heart J 2007;153: 831–6. [3] Peberdy MA, Kaye W, Ornato JP, et al. Cardiopulmonary resuscitation of adults in the hospital: a report of 14720 cardiac arrests from the National Registry of Cardiopulmonary Resuscitation. Resuscitation 2003;58:297–308.
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