Eur J Cardiothorac Surg 2006;30:617-620
© 2006 Elsevier Science NL
Creatine kinase isoenzyme MB relative index as predictor of mortality on extracorporeal membrane oxygenation support for postcardiotomy cardiogenic shock in adult patients
Ruoyu Zhang*,
Theo Kofidis,
Hiroyuki Kamiya,
Malakh Shrestha,
Rene Tessmann,
Axel Haverich,
Uwe Klima
Division of Thoracic- and Cardiovascular Surgery, Hannover Medical School, Carl-Neuberg Str. 1, 30625 Hannover, Germany
Received 5 May 2006;
received in revised form 16 July 2006;
accepted 17 July 2006.
* Corresponding author. Tel.: +49 511 532 6582; fax: +49 511 532 5404. (Email: Zhang.Ruoyu{at}mh-hannover.de).
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Abstract
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Objective: Extracorporeal membrane oxygenation (ECMO) has been used as initial, biventricular circulatory support for patients with severe postcardiotomy cardiogenic shock (PCS). Due to its aggressiveness and limited weaning quote, concerns have been raised about maintenance of ECMO support regarding duration. However, it is frequently hazardous for physicians to make an individualized decision, whether and when discontinuation of ECMO support should be considered. We tried to find measurable values during ECMO support that could predict the patient mortality on ECMO support. Methods: During a 9-year period, 32 patients (mean age 55.4 ± 11.9; ranging from 30 to 75 years) with ECMO support for postcardiotomy cardiogenic shock were included in this study. Results: Eighteen patients died without weaning (group I, 56.25%), while 14 patients could be weaned off the ECMO support (group II, 43.75%). In the group II, six patients (18.75%) died later in the postoperative course and eight patients (25%) survived to be discharged from hospital. The overall survival of all 32 patients at 30 days was 31.25% (n
= 10). At a follow-up period of 3.88 ± 1.58 years, the overall survival rate was 12.5% (n
= 4). Mean duration of ECMO support was 2.7 ± 1.7 days. The following variables were significantly different between the two groups: blood lactate level and the level of MB isoenzyme of creatine kinase (CK-MB) 48 h after ECMO initiation (p
< 0.01, p
= 0.001) as well as the CK-MB relative index as the ratio of CK-MB to total CK (p
< 0.001). Logistic regression identified that only the CK-MB relative index 48 h after ECMO initiation was associated with mortality on ECMO support (p
= 0.011, odds ratio = 1.219, 95% confidence interval: 1.046–1.421). Conclusion: For adult non-transplantation patients with postcardiotomy cardiogenic shock, the CK-MB relative index 48 h after ECMO initiation can be a predictor of mortality on ECMO support. This might be a useful tool for considering a patient either for discontinuation of ECMO support or further treatment.
Key Words: ECMO • Postcardiotomy cardiogenic shock • CK-MB relative index • Extracorporeal circulation
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1. Introduction
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Three to five percent of routine cardiac surgical procedures may be complicated with postcardiotomy cardiogenic shock (PCS) [1]. Approximately 1% of these patients require postoperative mechanical circulatory support (MCS) owing to refractory cardiac dysfunction not amenable to inotropic drugs and intraaortic balloon pumps [2,3]. Biventricular failure was common in patients with PCS [4,5]. Pennington et al. [6] reported that biventricular assistance was necessary in up to 50% of postcardiotomy patients who required MCS. Successful use of HeartMate VAD and Thoratec VAD for PCS has been reported [5,7]. However, due to technical complexity, these VADs are not suitable for critical patients as rescue therapy [8]. In comparison, extracorporeal membrane oxygenation (ECMO) provides a temporary means of biventricular circulatory support and substitute for lung function [9]. During surgery, ECMO can be easily applied through the cannula also used for cardiopulmonal bypass. It can also be quickly set up as femoral–femoral bypass at the bedside in the ICU. Therefore, the ECMO support has been used in our institution as initial, biventricular circulatory support, giving clinicians time for medical decision. If the right ventricle has been restored and patients may benefit from further aggressive treatment, left ventricular assist device (LVAD) as medium- or long-term circulatory support for the left ventricle may be required.
Although advances in technique and management were achieved, the weaning quote of ECMO therapy is still not better than 31–60% [10,11]. The complications of ECMO therapy are bleeding, stroke, infection and sepsis, requirement for dialysis, as well as distal limb ischemia [10,12]. Concerns have been raised about maintenance of ECMO support regarding duration, also according to the high costs [13]. However, specific guidelines are still missing. On the other hand, the optimal timing for conversion from ECMO to LVAD is still controversial. In this study, we reviewed our institution's experience with ECMO support and tried to find measurable values that may predict the mortality on ECMO support. These values could be of great importance for ICU-decision making and further treatment.
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2. Materials and methods
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2.1 Patients
Between January 1996 and October 2004, 32 adult non-transplantation patients (18 men, 14 women; mean age 55.4 ± 11.9, ranging from 30 to 75 years) required ECMO support for PCS in our institution. The cardiac operations included CABG (n
= 5), CABG and valvular operations (n
= 10), CABG and ventricular aneurysmectomy (n
= 2), valvular operations alone (n
= 10), pulmonary thromboendarterectomy (n
= 2), pericardectomy (n
= 1), resection of heart tumor (n
= 1), and aortic operation alone (n
= 1).
The patients were grouped as follows: group I (n
= 18), death on the ECMO support without weaning off; and group II (n
= 14), weaning off ECMO. The group II includes eight patients weaned and survived to be discharged from the hospital, and six patients weaned, but died later in the postoperative course.
2.2 Extracorporeal membrane oxygenation circuit
The ECMO perfusion system consisted of a centrifugal pump, BP-80 (Medtronic, Minneapolis, MN, USA) and an oxygenator, Hilite 7000LT (Medos, Stolberg, Germany) and a heat exchanger. The arterial return cannula was inserted directly either into the ascending aorta (13 patients), or into the femoral artery (17 patients), or into the subclavian artery (2 patients). Venous drainage was achieved from the right atrium (13 patients) or from the femoral vein (19 patients).
2.3 ECMO management strategy
The ECMO blood flow was adjusted to achieve a mixed venous oxygen saturation (SvO2) of 65–70%; oxygen flow (FiO2) was titrated to maintain a postoxygenator partial oxygen pressure of 300 mmHg or greater. Carbon dioxide was kept within the normal range (37–45 mmHg). During ECMO support, intravenous heparin was administered continuously and titrated to achieve an activated clotting time of 160–180 s. The oxygenator was monitored closely for the development of clots and was changed immediately if perfusion pressures started to increase. Platelets were administered to maintain a platelet count more than 105/µl. Fresh frozen plasma, coagulation factors, and antithrombin III were administered as required.
Mechanical ventilation was continued throughout the ECMO support with biphasic positive airway pressure. Ventilator setting was most commonly set at a tidal volume of 10 ml/kg, 10–12 breaths/min, positive end expiratory pressure of 10 cmH2O, a maximum ventilation pressure of 23 cmH2O.
Inotropic agents were reduced to a minimum to allow for optimal myocardial recovery while still maintaining left ventricular ejection. Norepinephirne was used to correct low peripheral vascular resistance and to maintain a mean arterial blood pressure of 70–80 mmHg. Intraaortic balloon pump support was employed in 10 patients to decrease afterload, increase coronary perfusion and pulsatility.
2.4 Statistical analysis
Descriptive statistics are presented as mean ± standard deviation. All statistical evaluation was performed using the SPSS (version 11.0 for Windows; SPSS Inc., Chicago, IL, USA). Statistical significance was assumed if p
< 0.05. Categorical variables are expressed as percentages and were evaluated with the Fischer's exact test. Continuous variables were evaluated by Student's t-test. Stepwise logistic regression analysis was used to determine the independent predictors for mortality of patients on the ECMO support.
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3. Results
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Among the 32 patients included in the study, 18 patients (56.25%, group I) were not able to wean off and died on the ECMO support. Fourteen patients (43.75%, group II) weaned from ECMO support. Eight patients in the group II (n
= 8, 25%) survived to be discharged from hospital, six patients in the group II (n
= 6, 18.75%) could be weaned off the ECMO support due to the initial improvement of cardiac function, but died later in the postoperative course due to multiple organ failure (n
= 3), brain death (n
= 2), or sudden death (n
= 1). The overall survival of all 32 patients at 30 days was 31.25% (n
= 10). At a follow-up period of 3.88 ± 1.58 years, the overall survival rate was 12.5% (n
= 4). Mean duration of ECMO support was 2.7 ± 1.7 days. ECMO-associated complications were bleeding (n
= 10, 31.25%) and limb ischemia (n
= 5, 15.63%).
Demographics and the preoperative risk profile of the patients are illustrated in Table 1
. There were no statistically significant differences between the two groups except the preoperative left ventricular ejection fraction (p
= 0.01). The intraoperative and postoperative parameters are illustrated in Table 2
. There were no significant differences between the two groups according to cross-clamp time, cardiopulmonary bypass time, use of IABP, and time of ECMO initiation after cardiac surgery. The blood lactate level 48 h after ECMO initiation (p
< 0.01), the MB isoenzyme of creatine kinase (CK-MB) 48 h after ECMO initiation (p
= 0.01), and the CK-MB relative index 48 h after ECMO initiation as the ratio of CK-MB to total CK (p
< 0.001) had statistically significant differences between the two groups. Logistic regression analysis revealed the CK-MB relative index 48 h after ECMO initiation to be a significant predictor of mortality on ECMO support (p
= 0.011, odds ratio = 1.219, 95% confidence interval: 1.046–1.421). The scatter graphic presented in Fig. 1
reveals the relation of CK-MB relative index 48 h after ECMO initiation to predicted probability of mortality on ECMO support. The predicted probability of mortality on ECMO therapy would be 50%, if the CK-MB relative index 48 h after ECMO initiation has a value of 11.26%.
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Fig. 1. The sigmoid curve indicates the correlation between CK-MB relative index 48 h after ECMO initiation and increasing mortality on the ECMO support.
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4. Discussion
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ECMO support is a proven technology that provides short-term, biventricular circulatory support to patients presenting postcardiotomy cardiogenic shock. After 5–7 days of ECMO support, few patients demonstrated significant further improvement in cardiac function and most begin to demonstrate progressive evidence of multiple organ failure [14]. In theory, the patients with a large perioperative myocardial injury are less likely to wean off ECMO, than those with a smaller injury. But specific guidelines for the therapy maintenance regarding duration are missing to help physicians making an individualized decision, whether and when discontinuation of ECMO support should be considered. In this study, we tried to find measurable values during ECMO support that could predict patient mortality on ECMO support.
The present study reports the outcome of 32 consecutive patients on ECMO support for postcardiotomy cardiogenic shock. Eighteen patients (56.25%) were not able to wean off and died on the ECMO support. Fourteen patients (43.75%) weaned from ECMO support. Among them, eight patients (25%) survived to be discharged from hospital, six patients (18.75%) could be weaned off the ECMO support, but presented intrahospital death. The overall survival of all 32 patients at 30 days was 31.25%. At a follow-up period of 3.88 ± 1.58 years, the overall survival rate was 12.5%. Mean duration of ECMO support was 2.7 ± 1.7 days. These results are comparable with reported in Refs. [5,12]. The patients, who did not wean from ECMO support, exhibited lower preoperative left ventricular function and high blood levels of lactate and CK-MB 48 h after ECMO initiation. But they are not correlated with the probability of patient mortality on ECMO support. An individualized decision for discontinuation of ECMO support cannot be made with these three parameters. In contrast, the CK-MB relative index 48 h after ECMO initiation exhibits a significant correlation to patient mortality on the ECMO support and might be a significant predictor of mortality of patients on ECMO support.
The CK-MB in plasma has been a feasible molecular marker of choice for the evaluation of myocardial injury. In skeletal muscle, CK-MB can comprise up to 2% of total CK while in cardiac muscle, CK-MB makes up 20–46% of total CK [15]. By expressing the CK-MB result as a percentage of total CK, it is possible to differentiate myocardial form skeletal muscle damage. Therefore, the CK-MB relative index as the ratio of CK-MB to total CK has a high specificity and much better utility for detection of myocardial injury [16,17]. However, the use of CK-MB relative index may not be appropriate in all cases, especially with low total CK results [17].
As limitation, this study is based on our single-center experience, and the included patients of this study are not many. However, outcomes correspond to those published elsewhere and the statistic analysis still revealed a significant result.
In summary, CK-MB relative index 48 h after ECMO initiation can be a feasible parameter for physicians to make the risk stratification of the patients on the ECMO support. According to the CK-MB relative index 48 h after ECMO initiation, decision can be supported, whether discontinuation of ECMO support can be considered.
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Abstract
1. Introduction
