Combining ECMO with IABP for the Treatment of Critically Ill Adult Heart Failure Patients

Transcription

1 Heart, Lung and Circulation (2014) 23, /04/$ ORIGINAL ARTICLE Combining ECMO with IABP for the Treatment of Critically Ill Adult Heart Failure Patients Pengyu Ma, MS a,1, Zaiwang Zhang, MS b,1, Tieying Song, MS a*, Yunliang Yang, MS a, Ge Meng, MD c, Jianhui Zhao, MS a, Chunping Wang, MS a, Kunfeng Gu, MS a, Jingyan Peng, MS a, Bo Jiang, MS a, Yan Qi, MS a, Ruyu Yan, MS d, Xiaojing Ma, MS a a Department of Anesthesiology, The First Hospital of Shijiazhuang, No. 36 Fanxi Road, Chang an District, Shijiazhuang , Hebei Province, China b Department of Anesthesiology, The Bethune International Peace Hospital of PLA China, No. 398 Zhongshan West Road, Shijiazhuang , Hebei Province, China c Department of Cardiac Surgery, The First Hospital of Shijiazhuang, No. 36 Van West Road, Shijiazhuang , China d Graduate School, Hebei Medical University, No. 361 Zhongshan East Road, Shijiazhuang , China Received 19 July 2013; received in revised form 22 September 2013; accepted 14 October 2013; online published-ahead-of-print 23 October 2013 Objective To discuss the experience of combining extra-corporeal membrane oxygenation (ECMO) with intra-aortic balloon pump (IABP) for the treatment of acute heart failure in critically ill adults. Methods The clinical data of 54 patients who received ECMO combined with IABP due to acute heart failure between January 2008 and July 2012 were retrospectively analysed. Thirty-eight of the patients were male, and 16 were female; the mean age was Thirty-nine of the patients received IABP first but were still unable to maintain adequate circulation, and were then given ECMO; the other 15 underwent ECMO first, but due to increased left ventricular load, the opening of the aortic valve was restricted and IABP was then introduced. Results Thirty-four patients (63%) were successfully weaned from ECMO; 21 patients (38.9%) survived to discharge. Major complications that occurred were renal failure (27 cases), infection (20 cases), blood plasma leakage in the oxygenator (13 cases), bleeding (18 cases), limb ischaemia (eight cases), and neurological complications (seven cases); in the group of patients who did not survive, the rates of bleeding occurrence, infection and renal failure were markedly higher than in the survived patients group. In both groups, the longer the patients were on support, the more improvement they showed in terms of MAP, CVP, Lac, SvO 2 and IS. Conclusion ECMO and IABP may have synergistic effects and play complementary roles in the treatment of acute cardiac failure; with timely administration, active prevention and treatment of complications, they can improve treatment outcome. Keywords Extracorporeal membrane oxygenation Intra-aortic balloon pump Acute heart failure Synergistic effects Central venous pressure *Corresponding author. Tel.: ; fax: , songtieyingbm@163.com 1 These authors contributed equally to this work Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier Inc. All rights reserved.

2 364 P. Ma et al. Introduction The IABP is a device which increases aortic root pressure during diastole by enhancing blood flow into the coronary arteries, thus increasing blood supply to the cardiac muscle; meanwhile, it decreases the pressure in the aorta during systole, reducing left ventricular afterload and thus reducing cardiac muscle oxygen consumption. These effects allow the weakened heart to recover its function. IABP can improve blood flow to internal organs to a certain extent, while increasing cardiac output by 10 20% [1], thus providing indispensable assistance in meeting the body s metabolic needs. IABP is currently the most commonly used mechanical circulatory support device in the treatment of acute heart failure; when administered in a timely manner, it can play a critical role in the rescue of patients with acute ischaemic myocardial infarctions [2,3]. Despite this, IABP cannot replace the physiological pumping of the heart; for patients whose cardiac muscle is already severely damaged, IABP support may not raise cardiac output sufficiently to meet the body s needs, creating the necessity for further circulatory support. The working principle of ECMO is to draw a portion of the body s blood outside of the body, oxygenate it, and then return it to the circulation; this improves oxygen supply throughout the body, providing some compensation for the reduction in cardiac output caused by impaired heart function and improving blood flow to tissues and organs. Furthermore, the veno-arterial type of ECMO can reduce cardiac preload by diverting blood flow, reducing cardiac oxygen demand even more; therefore ECMO can be used to treat acute heart failure. ECMO can also be used to treat acute lung failure; for example, when ECMO is applied to treatment of patients with acute respiratory distress syndrome (ARDS), it can effectively increase blood oxygen content and ensure sufficient oxygen transport [4]. However, for the venous-femoral arterial modality, when ECMO flow is increased, there is a corresponding increase in left ventricular afterload, which, when severe, can restrict the opening of the aortic valve, affecting left ventricular ejection and possibly lead to thrombus formation in the left ventricle [5,6]. In the venous-ascending aortic modality, on the other hand, continuous non-pulsating blood flow may reduce aortic root pressure during diastole, affecting blood supply to the cardiac muscle. Due to the limitations of both methods, neither IABP nor ECMO alone can achieve ideal outcomes in patients with severe disease [7], while combining them can in principle have a synergistic and complementary effect. The goal of this article is to discuss the clinical experience of combining ECMO with IABP for the treatment of acute heart failure in adults. Materials and Methods Patients In the period from January 2008 to July 2012, a total of 54 adult patients with acute heart failure received combined Table 1 Baseline Demographics of the Patients (n = 54). Subgroup Mean W SD Age dp/dt MAP (mmhg) 50 6 Subgroup N (%) LVEF < 0.45 (%) 41 (76) NYHA class (%) II 9 (18.8) III 29 (53.7) IV 16 (29.6) Complication Diabetes (%) 18 (33.3) Creatinine clearance rate < 80 ml/min (%) 18 (33.3) Child Pugh >7 (%) 18 (33.3) Coronary arterial disease 44 (81.5) Angina pectoris CCS class II 8 (14.8) III 24 (44.5) IV 12 (22.2) Myocardial infarction history 13 (24.1) Valve disease 14 (25.9) Left ventricular end-diastolic diameter (mm) >70 5 (9.3) <40 3 (5.6) ECMO and IABP support at our hospital. Thirty-eight were male, 16 were female, and the mean age was (with a range of 24 75). The basic demographics of all patients are shown in Table 1. The surgical operations they received are shown in Table 2. In our study 39 patients received IABP first but could not maintain adequate circulation, and were then treated with ECMO; 15 patients underwent ECMO first, and received IABP later due to the aortic valve restriction brought on by increased left ventricular afterload. The research was approved by the Ethical committee of the first hospital of Shijiazhuang and informed consent was obtained from all participants. IABP Placement Method For all patients, the femoral artery was cannulated for balloon placement (Seldinger method). The tip of the balloon was placed 1 cm distal to the junction with the left subclavian artery. After the operation, an X-ray was used to verify balloon positioning; 40 ml balloons were used in all patients. IABP Maintenance Either ECG or aortic pressure was used as a trigger; for the ECGs, the descending section of the R wave (representing closing of the aortic valve) was used to calibrate the counterpulsation interval, with a counterpulsation ratio of 1:1. If the patient showed low dependence on positive inotropic

3 Acute Heart Failure Treatment 365 Table 2 Surgical Procedures and Temporal Order of Treatments (n = 54). Operation Number IABP + ECMO ECMO + IABP CABG alone CABG + valvular operation CABG + remoulding of left ventricle CABG + radiofrequency ablation 2 2 CABG + repairing of ventricular Septal perforation 3 3 Heart Transplant 1 1 Fulminant myocarditis 1 1 Valvular operation drugs, the counterpulsation ratio was gradually reduced to 1:4 accompanied by half an hour of observation; if circulation was steady, the IABP was removed. ECMO Modality For all patients the veno-arterial (V-A) modality was employed. The centrifugal pump used was the Medtronic Bio-Console (Medtronic Heparin-coated Tube Set, CARMEDA coated oxygenator, and Maquet ECMO2050 artificial support pump). Fifty-two patients underwent venousfemoral arterial ECMO, while two patients underwent venous-ascending aortic ECMO. ECMO Maintenance During ECMO a waterbed was used to maintain patient body temperature between 36 8C and 37 8C. Venous drainage negative pressure was maintained within 30 mmhg; the oxygenator membrane absorbed oxygen at a concentration of 60%; ECMO flow was between 2 and 4 L/min, typically around 2.5 L/min; heparin was administered as an anticoagulant, maintaining an activated coagulation time (ACT) of s and a platelet count above 50,000. During the support period, the positive inotropic drug dosage was reduced. The mechanical respiration mode employed was volume controlled or synchronised intermittent mandatory ventilation plus pressure support (SIMV + PS); for patients with poor lung compliance and high airway pressure, pressure controlled ventilation (PCV) was used. Respiratory rate was set at 8 15 breaths/min, with tidal volume of 6 10 ml/kg, pressure support of 10 cm H 2 O, inspired oxygen concentration of 40 50% and peak airway pressure of 20 cm H 2 O; a value <8 mmhg of positive pressure was applied at the end of respiration to maintain alveolar expansion. Before weaning patients off ECMO, their condition was completely evaluated, positive inotropic drug dosage was adjusted to an appropriate level, respirator parameters were adjusted, and then ECMO flow was reduced; once it reached L/min or below, the patient was observed for half-an-hour, and if circulation was stable, the machine was stopped and cannulae were removed. Echocardiography and chest X-ray examinations were performed daily to dynamically observe heart and lung functions; the patient s blood, blood gases and various biochemical markers were also routinely examined. Respiratory monitoring was increased; any cardiac arrhythmia was corrected; the patient s internal homeostasis was maintained and supporting therapy was strengthened. All operations were strictly sterile and blood transportation to the body and limbs was closely observed. Once the patient was stable, weaning was done as soon as possible to prevent respiratory complications and other related complications. Data Collection Data were collected at the following time points: upon patients return to the intensive care unit (ICU) or right before simultaneous ECMO and IABP treatment was established (T1), 12 h later (T2), 24 h later (T3), and 48 h later (T4). The following data were collected: mean arterial pressure (MAP), central venous pressure (CVP), blood lactose (Lac), mixed venous oxygen saturation (SvO 2 ) and inotropic equivalence (IE) score [8]. Statistical Analysis The SPSS 13.0 statistical program was utilised for statistical analysis. Quantitative data are shown as mean with standard deviation (x sd). Continuous variables at different time points were examined with paired t-tests, with P < 0.05 considered statistically significant. Results 1. Survival Rates and Prognosis Thirty-four patients (63%) were successfully weaned from mechanical life support (weaned group); of these patients, 13 (24%) died from various complications after weaning, while 21 (39%) survived to discharge. Twenty patients (37%) were not weaned from mechanical circulatory support (unweaned group); 14 of these patients (26%) died due to inability of the heart to recover its function, while six (11%) were taken off support when family members decided to forego treatment. Discounting the six patients taken off treatment, the combination treatment with both mechanical circulatory support methods produced a survival rate of 44%. Mean ECMO support time was 59 h (ranging from 8 to 106 h);

4 366 P. Ma et al. Table 3 Complications (Number of Occurrences, Percentage of Total). Type of Complication Survival Group (n = 21) Mortality Group (n = 27) Occurrences Percentage (%) Occurrences Percentage (%) Renal failure * Bleeding * Infection * Oxygenator leakage Limb Thrombosis Neurological * P < 0.05 in comparison with the survival group. Table 4 Various Markers Before and After Support. Marker T1 T2 T3 T4 MAP (mmhg) Weaned (n = 34) ** 61 3** 66 5** Un-weaned (n = 14) ~~ 54 4 ~~ 50 3 ~~ CVP (mmhg) Weaned (n = 34) ** 15 2** 13 1** Un-weaned (n = 14) 21 2 ~~ 20 2* ~~ 19 3** ~~ 18 4** ~~ Lac (mmol/l) Weaned (n = 34) * ** ** Un-weaned (n = 14) * ** ~~ ** ~~ SvO 2 (%) Weaned (n = 34) ** 72 5** 73 4** Un-weaned (n = 14) ** ~~ 65 6** ~~ 61 7 ~~ IS (mg kg S1 min S1 ) Weaned (n = 34) ** 17 4** 12 3** Un-weaned (n = 14) ~~ 22 3** ~~ 21 4** ~~ Note: Compared with T1 of the same group *P < 0.05, **P < 0.01; Comparison between the two groups at the same time point ~ P < 0.05, ~~ P < mean IABP support time was 76 h (ranging from 8 to 252 h); mean ICU time was seven days. 2. Complications Not counting the six patients taken off treatments, within the other 48 patients there was a total of 93 occurrences of complications related to the mechanical circulatory support. There were 27 occurrences of renal failure (29%), 20 occurrences of infection (22%), 13 occurrences of blood plasma leakage in the oxygenator (14%), 18 occurrences of bleeding (19%), eight occurrences of limb ischaemia (9%), and seven occurrences of CNS complications (7%). In the 21 patients who were successfully weaned from mechanical circulatory support (survival group) there was a total of 35 occurrences of complications; in the 27 patients who did not survive (mortality group) there was a total of 58 occurrences of complications. In the mortality group, the rates of bleeding, infection, and renal failure occurrence were markedly higher than in the survival group with statistical significance, P < 0.05 (Table 3). Renal function impairment was observed in 27 patients and 24 of these patients received renal replacement therapy. 3. Overall, longer time on support was correlated with improved MAP, CVP, Lac, SvO 2, and IS. The weaned group showed greater improvement in all these markers compared to the un-weaned group; the difference was statistically significant, P < 0.05 (Table 4). Discussion There were 54 patients initially included in this study and all of them showed improvements in terms of overall circulation in addition to vasoactive drug applications; the rate of effectiveness was 100%. Thirty-four of the patients were successfully weaned from mechanical circulatory support, and 21 patients survived to discharge (39% of the total patient number). This shows that a combination of ECMO and IABP can

5 Acute Heart Failure Treatment 367 be used to treat patients with serious symptoms after heart surgery and there is an advantage in allowing the two methods to complement each other. Beside the six patients in the study not counted because of terminated treatments, there were 48 patients with a total of 93 complications. IABP and ECMO may lead to bleeding, infection, renal failure, peripheral blood vessel damage, haemolysis and other adverse events [9,10]. The overall major complications were 56% renal failures, 38% bleedings, 41% infections and 27% oxygenator leakages, which is in agreement with data from a recently published meta-analysis of 1763 ECMO treatments (52% renal failures, 33% bleedings, 33% bacterial pneumonia and 26% sepsis cases as well as 29% oxygenator dysfunctions) [11]. Bleeding was the most common complication occurring in the early stages of mechanical circulatory support and in this study there were 18 occurrences of bleeding, making up 19% of all complications. The bleeding most often occurred at the site of operation or in the digestive tract. The 21 patients who survived had less mechanical circulatory support-related complications compared to the 27 patients who died. Renal failure was the complication with the highest overall incidence rate, making up 29% of all complications. Renal failure under mechanical circulatory support is often the result of multiple factors: mechanical circulatory support is often a last resort after drug treatment has proven to be ineffective, so at this point the patient s heart and lungs are already severely damaged and the high dose of vasoconstrictive drugs leads to reduced blood flow to the kidneys and a markedly lower glomerular filtration rate. In our study there were 27 occurrences of renal damage and 24 patients underwent renal replacement therapies. Limb ischaemia made up 9% of the complications in this study: during cannulation of the femoral artery and vein, if the patient has atherosclerosis or narrow blood vessels or if an inappropriate model of cannula is used, peripheral blood vessel damage may occur [12]. Therefore, to reduce the occurrence of limb ischaemia, an appropriate model of cannula should be chosen and a bypass between the site of cannulation on the femoral artery and the distal end of the artery should be established in order to ensure adequate blood supply to the distal end [13]. IABP and ECMO both may lead to a reduced platelet count; when the flow rate is high, ECMO causes significant damage to red blood cells, showing up as increased free haemoglobin content in the serum and hyperbilirubinaemia. Regarding the order in which IABP and ECMO should be employed, there is currently no clear-cut answer, as there is a lack of randomised clinical trials on this subject. IABP can increase blood supply to the coronary arteries and reduce cardiac afterload and also causes less damage while requiring less anticoagulation medication; for ischaemic heart disease patients who still retain a certain amount of heart function, IABP can be implemented first, and ECMO can be added if circulation still cannot be adequately maintained [14]. For patients with severe heart damage and significantly altered cardiac structure, ECMO should be considered first in order to reduce patients traumata and medical costs. Despite treatment with combined IABP and ECMO, the in hospital death rate in this study was still 56.3%. The major reasons for failed mechanical support include: (1) Original heart disease was too severe and heart function could not be recovered. In this study, the weaned group showed greater improvement in MAP, CVP, Lac, SvO 2, and IS than the unweaned group, showing that mechanical support failed in some patients because their original heart disease condition was more severe. (2) Mechanical circulatory support was introduced too late and damage to the cardiac muscle and critical organs such as the liver and kidneys were already irreversible. (3) Occurrence of severe complications. In this study, 13 patients (24%) were successfully weaned from mechanical support, but died from complications such as infection, liver and kidney failure as well as CNS complications. Taken together, this suggests that for post-operational patients with severe heart disease, once there is clear indication for the procedure, mechanical circulatory support should be established in a timely manner in order to prevent an increase in death rate due to delayed treatments [15,16]; complications related to mechanical circulatory support should be prevented as much as possible to further increase the survival rate. There is already evidence that in terms of working principle, ECMO and IABP are synergistic and complementary to each other [16]. In this study, the longer the patients were on support, the more improvement they showed in terms of MAP, CVP, Lac, SvO 2 and IS. Therefore, when either method of mechanical circulatory support used alone is ineffective for treating acute heart failure patients in severe conditions, the two methods can be combined in a timely manner to improve the chances of a successful rescue; at the same time, actively preventing and treating related complications can further improve prognosis. Conflict of Interest No conflicts of interest declared. Acknowledgements We specially thank Professor Ming Jia from the Capital Medical University affiliated Beijing Anzhen Hospital for his support. References [1] Hedayati N, Sherwood JT, Schomisch SJ, Carino JL, Cmolik BL. Circulatory benefits of diastolic counterpulsation in an ischemic heart failure model after aortomyoplasty. J Thorac Cardiovasc Surg 2002; 123: [2] Di Russo GB, Martin GR. Extracorporeal membrane oxygenation for cardiac disease: no longer a mistaken diagnosis. Semin Thorac Cardiovasc Surg Pediatr Card Surg Annu 2005; [3] Schmidt M, Tachon G, Devilliers C, Muller G, Hekimian G, Brechot N, et al. Blood oxygenation and decarboxylation determinants during venovenous ECMO for respiratory failure in adults. Intensive Care Med 2013;39:

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