Int. J. Med. Sci. 2015, Vol. 12 http://www.medsci.org 306 International Journal of Medical Sciences 2015; 12(4): 306-311. doi: 10.7150/ijms.11343 Research Paper Using Vascular Closure Devices Following Out-OfHospital Cardiac Arrest? Martin Christ, Katharina Isabel von Auenmueller, Jeanette Liebeton, Martin Grett, Wolfgang Dierschke, Jan Peter Noelke, Irini Maria Breker, Hans-Joachim Trappe Department of Cardiology and Angiology, Marienhospital Herne, Ruhr University Bochum, Germany Corresponding author: Dr. med. Martin Christ, Department of Cardiology and Angiology, Marienhospital Herne, Ruhr University Bochum, Hoelkeskampring 40, 44625 Herne, Germany. Tel: (0049)-2323-499-5620; Fax: (0049)-2323-499-301; Email: martin.christ@marienhospital-herne.de 2015 Ivyspring International Publisher. Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited. See http://ivyspring.com/terms for terms and conditions. Received: 2014.12.14; Accepted: 2015.03.04; Published: 2015.03.28 Abstract Objectives and Background: Despite a generally broad use of vascular closure devices (VCDs), it remains unclear whether they can also be used in victims from out-of-hospital cardiac arrest (OHCA) treated with mild therapeutic hypothermia (MTH). Methods: All victims from OHCA who received immediate coronary angiography after OHCA between January 1st 2008 and December 31st 2013 were included in this study. The operator decided to either use a VCD (Angio-Seal) or manual compression for femoral artery puncture. The decision to induce MTH was based on the clinical circumstances. Results: 76 patients were included in this study, 46 (60.5%) men and 30 (39.5%) women with a mean age of 64.2 12.8 years. VCDs were used in 26 patients (34.2%), and 48 patients (63.2%) were treated with MTH. While there were significantly more overall vascular complications in the group of patients treated with MTH (12.5% versus 0.0%; p=0.05), vascular complications were similar between patients with VCD or manual compression, regardless of whether or not they were treated with MTH. Conclusion: In our study, the overall rate of vascular complications related to coronary angiography was higher in patients treated with mild therapeutic hypothermia, but was not affected by the application of a vascular closure device. Therefore, our data suggest that the use of VCDs in victims from OHCA might be feasible and safe in patients treated with MTH as well, at least if the decision to use them is individually carefully determined. Key words: out-of-hospital cardiac arrest, resuscitation, mild therapeutic hypothermia, coronary angiography, vascular closure device Introduction The current Guidelines of the European Resuscitation Council emphasise early coronary angiography in all post-cardiac arrest patients who are suspected of having coronary artery disease [1]. Several studies confirmed that the combination of mild therapeutic hypothermia (MTH) and early coronary angiography - inclusive percutaneous coronary intervention (PCI), if necessary - is feasible and safe in patients following out-of-hospital cardiac arrest (OHCA) [2-6]. However, although the use of vascular closure devices (VCDs) has increased during the past decade, no study has focussed on the safety of VCDs prior to MTH in victims from OHCA. Material and Methods Patients Altogether, 76 patients who received emergency coronary angiography within the first two hours after OHCA between January 1st 2008 and December 31st 2013 were included in this study. Mean age was 64.2 12.8 years. Patients data were collected from the patients health records and anonymously stored on a central Ivyspring International Publisher Int. J. Med. Sci. 2015, Vol. 12 http://www.medsci.org 307 database. Coronary angiography Catheterisation was performed according to standard techniques with the six French femoral approach. If a recent coronary-artery stenosis was found, coronary angioplasty was attempted, unless the artery was too small or the operator considered the procedure to be technically impossible. Standard resuscitative and stabilisation procedures were continued during the procedure if necessary. All patients who received percutaneous coronary intervention received 500 mg acetylsalicylic acid and 5.000 IU unfractionated heparin intravenously during PCI, and 600 mg clopidogrel immediately after placement of a nasogastric tube. Vascular closure device At the end of the procedure, the operator decided to use either a vascular closure device or manual compression for femoral artery puncture. If a VCD was chosen, an Angio-Seal device (St. Jude Medical, Minnetonka, MN, USA) that consists of an intra-arterially deployed polymer anchor, a collagen sponge positioned on the outer artery wall, and a self-tightening suture was used. The whole system is bioabsorbed within 90 days. All patients were followed-up by an experienced emergency physician. Hb-relevant bleeding was defined as a haemoglobin drop of more than 3 g/dl within the first 24 hours following coronary angiography and exclusion of other obvious causes or clinical bleeding signs. Mild therapeutic hypothermia The decision to induce MTH was based on the clinical circumstances, taking into account aspects like initial rhythm, duration of resuscitation, and state of consciousness. If necessary, MTH was induced immediately after the emergency coronary procedure with the CoolGard 3000 system since several studies confirmed the safety and effectiveness of intravascular cooling [7]. The target temperature was 33 Celsius for 24 hours, the rate of temperature change was maximised to induce MTH and was 0.3 Celsius/hour to rewarm the patients. The Cooling Catheter with the saline flowing within was placed via the femoral vein in the cardiac catheterisation laboratory at the end of the coronary procedure. Statistical analysis Statistical analysis was performed with the Statistical Package of Social Science (SPSS 22.0, IBM, Armonk, NY, USA). Continuous variables are expressed as the mean SD, and comparisons of categorical variables among groups were conducted using Chi-square tests or Students t-test. Data collection and analysis was approved by the local ethical review committee. Results All patients Of the 76 patients were included in our study, 46 (60.5%) were men and 30 (39.5%) were women, and a mean age of 64.2 12.8 years. Altogether, 60 events (78.9%) were witnessed, lay resuscitation was attempted in 43 events (56.6%), and 44 patients (57.9%) presented with an initial shockable rhythm. Of the 38 (50.0%) patients that presented with myocardial infarction, 27 (35.5%) presented with ST elevation myocardial infarction (STEMI) and 11 (14.5%) presented with non ST elevation myocardial infarction (NSTEMI). Coronary angiography confirmed coronary artery disease in 63 (82.9%) patients: 13 (17.1%) patients had one vessel disease, 17 (22.4%) patients had two vessel disease, and 33 (43.4%) patients had three vessel disease. Percutaneous coronary intervention was attempted in 53 (69.7%) patients, with the culprit lesion in the left anterior descendens (LAD) in 21 (27.6%) patients, in the Ramus circumflexus (RCX) in seven (9.2%) patients, in the right coronary artery (RCA) in 14 (18.4%) patients, and in a coronary artery bypass graft (CABG) in one (1.3%) patient, while 10 (13.2%) patients received multi-vessel intervention. If necessary, the duration of the coronary angiography and PCI was 50.0 31.0 minutes. In 17 (22.4%) patients, Eptifibatide was used during intervention. Angio-Seal devices were used in 26 (34.2%) patients, and six (7.9%) showed vascular complications, such as Hb-relevant bleeding (6.6%) or arterial occlusion (1.3%). Forty-one (53.9%) patients who received immediate coronary angiography after hospital admission survived until hospital discharge (Table 1). Comparison of patients treated with MTH and patients not treated with MTH 48 victims from OHCA (63.2%) were treated with mild therapeutic hypothermia after immediate coronary angiography, 28 patients (36.8%) were not. In comparison of both groups we observed significant more lay resuscitations in the group of patients not treated with MTH (45.8% vs 75.0%; p=0.01) and significant more overall vascular complications in the group of patients treated with MTH (12.5% vs 0.0%; p=0.05). No significant differences could be observed with regard on patients` gender, age, witnessed arrests, initial shockable rhythm, myocardial infarction, Int. J. Med. Sci. 2015, Vol. 12 http://www.medsci.org 308 prevalence of coronary artery disease, PCI attempt, duration of coronary angiography, use of eptifibatide during PCI, use of Angio-Seal and survival until hospital discharge (Table 1). Table 1: Patient characteristics from all patients (first column), patients treated with mild therapeutic hypothermia (MTH) following out-of-hospital cardiac arrest (OHCA; second column), and OHCA victims who were not treated with MTH (third column) All patients n = 76 Patients treated with MTH n = 48 Patients not treated with MTH n = 28 p Male gender 46 (60.5%) 29 (60.4%) 17 (60.7%) 0.98 Age (years) [range] 64.2 12.8 [3488] 62.3 13.7 [3488] 67.5 11.3 [4788] 0.09 Witnessed cardiac arrest 60 (78.9%) 38 (79.2%) 22 (78.6%) 0.81 Lay resuscitation 43 (56.6%) 22 (45.8%) 21 (75.0 %) 0.01 Initial shockable rhythm 44 (57.9%) 30 (62.5%) 14 (50.0 %) 0.37 Myocardial infarction 38 (50.0%) 25 (52.1%) 13 (46.4%) 0.92 ST elevation myocardial infarction (STEMI) 27 (35.5%) 19 (39.6%) 8 (28.6%) Non-ST elevation myocardial infarction (NSTEMI) 11 (14.5%) 6 (12.5%) 5 (17.9%) Coronary artery disease 63 (82.9%) 40 (83.3%) 23 (82.1%) 0.89 One vessel disease 13 (17.1%) 7 (14.6%) 6 (21.4%) Two vessel disease 17 (22.4%) 12 (25.0%) 5 (17.9%) Three vessel disease 33 (43.4%) 21 (43.8%) 12 (42.9%) Percutaneous coronary intervention (PCI) 53 (69.7%) 35 (72.9%) 18 (64.3%) 0.43 Left anterior descendens (LAD) 21 (27.6%) 16 (33.3%) 5 (17.9%) Ramus circumflexus (RCX) 7 (9.2%) 4 (8.3%) 3 (10.7%) Right coronary artery (RCA) 14 (18.4%) 8 (16.7%) 6 (21.4%) Multi vessel disease (MV) 10 (13.2%) 1 (1.3%) 6 (12.5%) 1 (2.1%) 4 (14.3%) 0 (0.0%) Coronary artery bypass graft (CABG) Use of Eptifibatide (Integrilin) 17 (22.4%) 12 (25.0%) 5 (17.9%) 0.47 Duration of coronary angiography (min) [range] 50.0 31.0 [7186] 48.3 27.0 [8132] 51.0 35.7 [7186] 0.71 Vascular closure device (Angio-Seal) 26 (34.2%) 16 (33.3%) 10 (35.7%) 0.83 Vascular complication 6 (7.9%) 6 (12.5%) 0 (0.0%) 0.05 Hb relevant bleeding 5 (6.6%) 5 (10.4%) - 0.08 conservative therapy 1 (1.3%) 1 (2.1%) - transfusion 3 (3.9%) 3 (6.3%) - operation + transfusion 1 (1.3%) 1 (2.1%) - Arterial occlusion 1 (1.3%) 1 (2.1%) - 0.44 operation 1 (1.3%) 1 (2.1%) - Survival until hospital discharge 41 (53.9%) 27 (56.3%) 14 (50.0%) 0.60 Comparison of patients treated with MTH who received Angio-Seal and those who did not Patients who were treated with MTH and received Angio-Seal presented less often with myocardial infarction (31.3% versus 62.5%; p=0.03), received less frequent percutaneous coronary intervention (50.0% versus 84.4%; p=0.01), were treated with eptifibatide less frequently (6.25% versus 34.4%; p=0.03), and coronary angiography was shorter (34.4 21.6 min versus 55.3 27.0 min; p=0.01) than in patients who did not receive an Angio-Seal device. No significant differences were observed with regard to the patients gender, age, witnessed arrests, lay-resuscitation, initial shockable rhythm, prevalence of coronary artery disease, vascular complications, or survival until hospital discharge (Table 2). Comparison of patients not treated with MTH who received Angio-Seal and those who did not In the victims who suffered from OHCA who were not treated with MTH, no differences could be observed between those patients who received an Angio-Seal and those patients who did not (Table 2). Discussion Mild therapeutic hypothermia In victims who suffered OHCA, the combination of MTH and early coronary angiography inclusive PCI, if necessary, has been described as feasible and safe [2-6]. Specifically, bleeding complications have been excluded as relevant clinical problems related to MTH in several previous studies [8-12]. However, bleeding rates varied enormously in the different studies. While Nielsen et al. [2] described an increased risk of bleeding in only 4% of all patients following OHCA if coronary angiography with (6.2%) or without PCI (2.8%) was performed, other studies reported much higher bleeding rates of more than 20% [6, 13, 14] and a tendency towards increased bleeding complications in the MTH-treated group, which we also observed in our data (p=0.08) (table 2) [6, 14]. The underlying mechanism for this observation is unknown. Coronary angiography per se affects coagulation [15], and therapeutic hypothermia may, depending on the depth and duration, induce coagulopathy [16]. Additionally, in an animal model, thrombelastometry at 34C during hypothermia showed significant differences for clotting time and clot formation [17]. Nevertheless, to our knowledge, there is no study that could further differentiate the influence of each of these individual factors. In addition, patients routinely receive heparin before coronary angiography and platelet inhibitors in association with PCI in a standard dose regardless of their post-resuscitation status. However, although it could be shown that MTH does not augment abciximab-induced inhibition of platelet aggregation [18], there are no reports on the influence of hypothermia on clopidogrel, prasugrel, or ticagrelor concentrations, and a potentially resulting risk of under- or overtreatment with these drugs in OHCA victims treated with MTH. Int. J. Med. Sci. 2015, Vol. 12 http://www.medsci.org 309 Table 2: Comparison of out-of-hospital cardiac arrest (OHCA) victims who received an Angio-Seal after coronary angiography and those who did not receive an Angio-Seal with special attention to additional treatment with mild therapeutic hypothermia Patients treated with MTH Patients not treated with MTH Angio-Seal n = 16 No Angio-Seal n = 32 p Angio-Seal n = 10 No Angio-Seal n = 18 p Male gender 8 (50.0%) 21 (65.6%) 0.30 5 (50.0%) 12 (66.7%) 0.39 Age (years) [range] 66.0 14.6 [3788] 60.4 13.0 [3487] 0.19 66.8 15.4 [4788] 67.9 8.7 [5385] 0.81 Witnessed cardiac arrest 13 (81.3%) 25 (78.1%) 0.13 7 (70.0%) 15 (83.3%) 0.14 Lay resuscitation 6 (37.5%) 16 (50.0%) 0.41 8 (80.0%) 13 (72.2%) 0.73 Initial shockable rhythm 8 (50.0%) 22 (68.8%) 0.21 6 (60.0%) 8 (44.4%) 0.52 Myocardial infarction 5 (31.3%) 20 (62.5%) 0.03 5 (50.0%) 8 (44.4%) 0.79 ST elevation myocardial infarction 5 (31.3%) 14 (43.8%) 3 (30.0%) 5 (27.8%) (STEMI) 0 (0.0%) 6 (18.8%) 2 (20.0%) 3 (16.7%) Non-ST elevation myocardial infarction (NSTEMI) Coronary artery disease 11 (68.8%) 29 (90.6%) 0.06 8 (80.0%) 15 (83.3%) 0.83 One vessel disease 2 (12.5%) 5 (15.6%) 0 (0.0%) 6 (33.3%) Two vessel disease 5 (31.3%) 7 (21.9%) 3 (30.0%) 2 (11.1%) Three vessel disease 4 (25.0%) 17 (53.1%) 5 (50.0%) 7 (38.9%) Percutaneous coronary intervention (PCI) 8 (50.0%) 27 (84.4%) 0.01 7 (70.0%) 11 (61.1%) 0.64 Left anterior descendens (LAD) 4 (25.0%) 12 (37.5%) 2 (20.0%) 3 (16.7%) Ramus circumflexus (RCX) 0 (0.0%) 4 (12.5%) 1 (10.0%) 2 (11.1%) Right coronary artery (RCA) 3 (18.8%) 5 (15.6%) 1 (10.0%) 5 (27.8%) Multi vessel disease (MV) 1 (6.3%) 5 (15.6%) 3 (30.0%) 1 (5.6%) Coronary artery bypass graft (CABG) 0 (0.0%) 1 (3,1%) 0 (0.0%) 0 (0.0%) Use of Eptifibatide (Integrilin) 1 (6.3%) 11 (34.4%) 0.03 1 (10.0%) 4 (22.2%) 0.42 Duration of coronary angiography (min) [range] 34.4 21.6 [893] 55.3 27.0 [15132] 0.01 58.5 54.4 [7186] 46.8 20.2 [1676] 0.42 Vascular complication 3 (18.8%) 3 (9.4%) 0.36 0 (0.0%) 0 (0.0%) n.a. Hb relevant bleeding 3 (18.8%) 2 (6.3%) 0.18 - - conservative therapy 1 (6.3%) 0 (0.0%) - - transfusion 1 (6.3%) 2 (6.3%) - - operation 1 (6.3%) 0 (0.0%) - - Arterial occlusion 0 (0.0%) 1 (3.1%) 0.48 - - operation - 1 (3.1%) - - Survival until hospital discharge 8 (50.0%) 19 (59.4%) 0.54 6 (60.0%) 8 (44.4%) 0.43 n.a.: not available Figure 1: Differences within the group of patients treated with vascular closure devices depending on whether they received mild therapeutic hypothermia (MTH) or not. Int. J. Med. Sci. 2015, Vol. 12 http://www.medsci.org 310 We therefore recommend that previous studies should try to verify whether some of these factors combined may increase the risk of bleeding, requiring transfusion when an invasive procedure is performed in resuscitated patients treated with MTH. Vascular closure devices Several studies describe the safety of vascular closure devices after routine coronary angiogram and routine PCI [19, 20], as well as following coronary interventions using anticoagulation and GP IIb/IIIa inhibitor therapy [21]. Therefore, the use of VCDs has increased during the last decade, especially since the application of VCDs has been described as independently associated with a reduction in the rate of vascular complications and the post-PCI length of hospital stay [22]. Nevertheless, there are also data that reported an increase in the serious risk for retroperitoneal bleeding in patients treated with VCDs [23]. Additionally, in contrast to elective settings, the risk of access site-related vascular complications was significantly increased after application of the VCD Angio-Seal in patients undergoing emergency catheterisations for NSTEMI/STEMI when compared with manual compression [24]. Since victims from OHCA undergo emergency catheterisation, VCDs should be used carefully in this group. However, no previous study focused specifically on this patient collective. In our study, VCDs were used in about one third (34.2%) of all OHCA victims (Table 1). Further subgroup analysis revealed that, at least in patients treated with MTH, the application of Angio-Seal devices was influenced by coronary findings, such as myocardial infarction, percutaneous coronary intervention, or treatment with GP IIb/IIIa inhibitor, with less frequent use of VCDs in more complex procedures (Table 2). However, the use of VCDs was not adapted for further treatment with MTH in general (Table 2, Figure 1). Regardless of whether the OHCA were treated with MTH after coronary angiography or not, we could not observe any difference in the rate of vascular complications or survival rates between patients treated with or without VCD (Table 2). Limitations The present study is a single center study and, therefore, our findings should be verified by further investigations. Conclusions In our study, the overall rate of vascular complications related to coronary angiography was higher in patients treated with MTH, but was not affected by the application of a VCD. Therefore, our data suggest that the use of VCDs in OHCA victims might be also feasible and safe in patients treated with MTH, at least if the decision to use them is carefully considered and adapted on an individual basis. Conflict of interest All authors declare no conflicts of interest. References 1. Nolan JP, Soar J, Zideman DA, et al. European Resuscitation Council Guidelines for Resuscitation 2010 Section 1. Executive summary. Resuscitation. 2010; 81: 1219-76. 2. Nielsen N, Hovdenes J, Nilsson F, et al. Outcome, timing and adverse events in therapeutic hypothermia after out-of-hospital cardiac arrest. Acta Anaesthesiol Scand. 2009; 53: 926-34. 3. Sunde K, Pytte M, Jacobsen D, et al. Implementation of a standardised treatment protocol for post resuscitation care after out-of-hospital cardiac arrest. Resuscitation. 2007; 73: 29-39. 4. Knafelj R, Radsel P, Ploj T, et al. Primary percutaneous coronary intervention and mild induced hypothermia in comatose survivors of ventricular fibrillation with ST-elevation acute myocardial infarction. Resuscitation. 2007; 74: 227-34. 5. Hovdenes J, Laake JH, Aaberge L, et al. Therapeutic hypothermia after out-of-hospital cardiac arrest: experiences with patients treated with percutaneous coronary intervention and cardiogenic shock. Acta Anaesthesiol Scand. 2007; 51: 137-42. 6. Wolfrum S, Pierau C, Radke PW, et al. Mild therapeutic hypothermia in patients after out-of-hospital cardiac arrest due to acute ST segment elevation myocardial infarction undergoing immediate percutaneous coronary intervention. Crit Care Med. 2008; 36: 1780-6. 7. Hinz J, Rosmus M, Popov A, et al. Effectiveness of an intravascular cooling method compared with a conventional cooling technique in neurologic patients. J Neurosurg Anesthesiol. 2007; 19: 130-5. 8. Hypothermia after Cardiac Arrest Study Group. Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. N Engl J Med. 2002; 346: 549-56. 9. Belliard G, Catez E, Charron C, et al. Efficacy of therapeutic hypothermia after out-of-hospital cardiac arrest due to ventricular fibrillation. Resuscitation. 2007; 75: 2529. 10. Laish-Farkash A, Matetzky S, Kassem S, et al. Therapeutic hypothermia for comatose survivors after cardiac arrest. Isr Med Assoc J. 2007; 9: 2526. 11. Oddo M, Schaller MD, Feihl F, et al. From evidence to clinical practice: effective implementation of therapeutic hypothermia to improve patient outcome after cardiac arrest. Crit Care Med. 2006; 34: 186573. 12. Sunde K, Pytte M, Jacobsen D, et al. Implementation of a standardised treatment protocol for post resuscitation care after out-of-hospital cardiac arrest. Resuscitation. 2007; 73: 2939. 13. Kozinski M, Pstragowski K, Kubica JM, et al. ACS network-based implementation of therapeutic hypothermia for the treatment of comatose out-of-hospital cardiac arrest survivors improves clinical outcomes: the first European experience. Scand J Trauma Resusc Emerg Med. 2013; 21: 22. 14. Zimmermann S, Flachskampf FA, Schneider R, et al. Mild therapeutic hypothermia after out-of-hospital cardiac arrest complicating ST-elevation myocardial infarction: long-term results in clinical practice. Clin Cardiol. 2013; 36: 414-21. 15. Bttiger BW, Motsch J, Bhrer H, et al. Activation of blood coagulation after cardiac arrest is not balanced adequately by activation of endogenous fibrinolysis. Circulation. 1995; 92: 2572-8. 16. Mayer S. Therapeutic hypothermia. New York, USA: Marcel Dekker; 2005. 17. Mohr J, Ruchholtz S, Hildebrand F, et al. Induced hypothermia does not impair coagulation system in a swine multiple trauma model. J Trauma Acute Care Surg. 2013; 74: 1014-20. 18. Frelinger AL III, Furman MI, Barnard MR, et al. Combined effects of mild hypothermia and glycoprotein IIb/IIIa antagonists on platelet-platelet and leukocyte-platelet aggregation. Am J Cardiol. 2003; 92: 1099101. 19. Lee SW, Tam CC, Wong KL, et al. Long-term clinical outcomes after deployment of femoral vascular closure devices in coronary angiography and percutaneous coronary intervention: an observational single-centre registry follow-up. BMJ Open. 2014; 4: e005126. 20. Gregory D, Midodzi W, Pearce N. Complications with Angio-Seal vascular closure devices compared with manual compression after diagnostic cardiac catheterization and percutaneous coronary intervention. J Interv Cardiol. 2013; 26: 630-8. 21. Applegate RJ, Grabarczyk MA, Little WC, et al. Vascular closure devices in patients treated with anticoagulation and IIb/IIIa receptor inhibitors during percutaneous revascularization. J Am Coll Cardiol. 2002; 40: 78-83. 22. Kerr S, Kustermans L, Vandendriessche T, et al. Cost-effectiveness of contemporary vascular closure devices for the prevention of vascular complications after percutaneous coronary interventions in an all-comers PCI population. EuroIntervention. 2014; 10: 191-7. Int. J. Med. Sci. 2015, Vol. 12 http://www.medsci.org 311 23. Gurm HS, Hosman C, Share D, et al. Comparative safety of vascular closure devices and manual closure among patients having percutaneous coronary intervention. Ann Intern Med. 2013; 159: 660-6. 24. Stegemann E, Hoffmann R, Marso S, et al. The frequency of vascular complications associated with the use of vascular closure devices varies by indication for cardiac catheterization. Clin Res Cardiol. 2011; 100: 789-95.

Int. J. Med. Sci. 2015, Vol. 12 http://www.medsci.org 306 International Journal of Medical Sciences 2015; 12 (4): 306-311. doi: 10,7150 / ijms.11343 Kertas Penelitian Menggunakan Vascular Penutupan Perangkat Mengikuti Out-OfHospital Jantung Penangkapan? Martin Kristus, Katharina von Isabel Auenmueller, Jeanette Liebeton, Martin Grett, Wolfgang Dierschke, Jan Peter Noelke, Irini Maria Breker, Hans-Joachim Trappe Departemen Kardiologi dan Angiology, Marienhospital Herne, Ruhr - Universitas Bochum, Jerman Sesuai penulis: Dr . med. Martin Kristus, Departemen Kardiologi dan Angiology, Marienhospital Herne, Ruhr - Universitas Bochum, Hoelkeskampring 40, 44625 Herne, Jerman. Telp: (0049) -2323-499-5620; Fax: (0049) -2323-499-301; Email: martin.christ@marienhospital-herne.de 2015 Ivyspring Penerbit. Reproduksi diperbolehkan untuk penggunaan pribadi, non-komersial, asalkan artikel tersebut secara keseluruhan, dimodifikasi, dan dikutip benar. Lihat http://ivyspring.com/terms untuk syarat dan kondisi. Diterima: 2014/12/14; Diterima: 2015/03/04; Diterbitkan: 2015/03/28 Tujuan Abstrak dan Latar Belakang: Meskipun penggunaan umumnya luas perangkat penutupan pembuluh darah (VCD), masih belum jelas apakah mereka juga dapat digunakan dalam korban dari out-of-rumah sakit serangan jantung (OHCA) diobati dengan terapi hipotermia ringan (MTH). Metode: Semua korban dari OHCA yang menerima langsung angiografi koroner setelah OHCA antara 1 Januari 2008 dan 31 Desember 2013 dilibatkan dalam penelitian ini. Operator memutuskan untuk baik menggunakan VCD (Angio-Seal ) atau kompresi manual tusukan arteri femoral. Keputusan untuk menginduksi MTH didasarkan pada keadaan klinis. Hasil: 76 pasien dilibatkan dalam penelitian ini, 46 (60,5%) laki-laki dan 30 (39,5%) wanita dengan usia rata-rata 64,2 12,8 tahun. VCD yang digunakan dalam 26 pasien (34,2%), dan 48 pasien (63,2%) diobati dengan MTH. Sementara ada secara signifikan lebih komplikasi vaskular keseluruhan pada kelompok pasien yang diobati dengan MTH (12,5% vs 0,0%; p = 0,05), komplikasi vaskular adalah serupa antara pasien dengan VCD atau kompresi manual, terlepas dari apakah atau tidak mereka diperlakukan dengan MTH . Kesimpulan: Dalam penelitian kami, tingkat keseluruhan komplikasi vaskular terkait dengan angiografi koroner lebih tinggi pada pasien yang diobati dengan terapi hipotermia ringan, tetapi tidak terpengaruh oleh penerapan perangkat penutupan pembuluh darah. Oleh karena itu, data kami menunjukkan bahwa penggunaan VCD di korban dari OHCA mungkin layak dan aman pada pasien yang diobati dengan MTH juga, setidaknya jika keputusan untuk menggunakannya secara individual hati-hati ditentukan. Kata kunci: out-of-rumah sakit serangan jantung, resusitasi, hipotermia terapeutik ringan, angiografi koroner, pembuluh darah Pendahuluan perangkat penutupan Pedoman saat ini Dewan Resuscitation Eropa menekankan angiografi koroner dini pada semua pasien serangan jantung pasca-yang diduga memiliki arteri koroner Penyakit [1]. Beberapa penelitian menegaskan bahwa kombinasi terapi hipotermia ringan (MTH) dan awal angiografi koroner - intervensi koroner perkutan inklusif (PCI), jika perlu - layak dan aman pada pasien berikut penangkapan out-of-rumah sakit jantung (OHCA) [2-6 ]. Namun, meskipun penggunaan perangkat penutupan pembuluh darah (VCD) telah meningkat selama dekade terakhir, tidak ada penelitian yang difokuskan pada keamanan VCD sebelum MTH di korban dari OHCA. Bahan dan Metode Pasien keseluruhan, 76 pasien yang menerima darurat angiografi koroner dalam waktu dua jam pertama setelah OHCA antara 1 Januari 2008 dan 31 Desember 2013 dilibatkan dalam penelitian ini. Usia rata-rata adalah 64,2 12,8 tahun. Pasien 'Data dikumpulkan dari pasien catatan kesehatan dan anonim disimpan pada pusat Ivyspring Penerbit Int. J. Med. Sci. 2015, Vol. 12 http://www.medsci.org 307 basis data. Koroner angiografi Kateterisasi dilakukan menurut teknik standar dengan enam pendekatan femoral Perancis. Jika stenosis koroner-arteri baru-baru ini ditemukan, angioplasti koroner dicoba, kecuali arteri itu terlalu kecil atau operator dianggap prosedur secara teknis tidak mungkin. Resusitasi dan stabilisasi prosedur standar dilanjutkan selama prosedur jika perlu. Semua pasien yang menerima intervensi koroner perkutan menerima 500 mg asam asetilsalisilat dan 5.000 IU tak terpecah heparin intravena selama PCI, dan 600 mg clopidogrel segera setelah penempatan tabung nasogastrik. Perangkat penutupan pembuluh darah Pada akhir prosedur, operator memutuskan untuk menggunakan perangkat penutupan pembuluh darah atau kompresi manual tusukan arteri femoral. Jika VCD dipilih, perangkat Angio-Seal (St Jude Medical, Minnetonka, MN, USA) yang terdiri dari dikerahkan anchor polimer-arterially intra, spons kolagen diposisikan pada dinding arteri luar, dan self-pengetatan jahitan digunakan. Seluruh sistem bioabsorbed dalam waktu 90 hari. Semua pasien ditindaklanjuti oleh dokter darurat berpengalaman. Perdarahan Hb-relevan didefinisikan sebagai penurunan hemoglobin lebih dari 3 g / dl dalam 24 jam pertama setelah angiografi koroner dan eksklusi penyebab jelas lainnya atau tanda perdarahan klinis. Hipotermia terapeutik ringan Keputusan untuk menginduksi MTH didasarkan pada keadaan klinis, memperhitungkan aspek seperti ritme awal, durasi resusitasi, dan negara kesadaran. Jika perlu, MTH diinduksi segera setelah prosedur koroner darurat dengan CoolGard 3000 sistem sejak beberapa penelitian mengkonfirmasi keamanan dan efektivitas pendinginan intravaskular [7]. Suhu target adalah 33 Celsius selama 24 jam, laju perubahan suhu yang dimaksimalkan untuk mendorong MTH dan 0,3 Celsius / jam untuk rewarm pasien. The Cooling Kateter dengan garam yang mengalir dalam ditempatkan melalui vena femoralis di laboratorium kateterisasi jantung pada akhir prosedur koroner. Analisis statistik Analisis statistik dilakukan dengan Paket statistik Ilmu Sosial (SPSS 22,0, IBM, Armonk, NY, USA). Variabel kontinu dinyatakan sebagai mean SD, dan perbandingan variabel kategori antara kelompok-kelompok dilakukan dengan menggunakan tes Chi-square atau t-test Student. Pengumpulan dan analisis data telah disetujui oleh komite peninjau etik lokal. Hasil Semua pasien Dari 76 pasien dilibatkan dalam penelitian kami, 46 (60,5%) adalah laki-laki dan 30 (39,5%) adalah perempuan, dan usia rata-rata 64,2 12,8 tahun. Secara keseluruhan, 60 kejadian (78,9%) yang menyaksikan, berbaring resusitasi dicoba di 43 peristiwa (56,6%), dan 44 pasien (57,9%) disajikan dengan irama shockable awal. Dari 38 (50,0%) pasien yang disajikan dengan infark miokard, 27 (35,5%) disajikan dengan elevasi ST infark miokard (STEMI) dan 11 (14,5%) disajikan dengan ST elevasi infark miokard non (NSTEMI). Angiografi koroner dikonfirmasi penyakit arteri koroner di 63 (82,9%) pasien: 13 (17,1%) pasien memiliki satu penyakit pembuluh, 17 (22,4%) pasien memiliki dua penyakit pembuluh, dan 33 (43,4%) pasien memiliki tiga penyakit pembuluh. Intervensi koroner perkutan dicoba di 53 (69,7%) pasien, dengan lesi pelakunya di descendens anterior kiri (LAD) di 21 (27,6%) pasien, di Ramus circumflexus (RCX) di tujuh (9,2%) pasien, di kanan arteri koroner (RCA) di 14 (18,4%) pasien, dan dalam koroner artery bypass graft (CABG) dalam satu (1,3%) pasien, sedangkan 10 (13,2%) pasien menerima intervensi multi-kapal. Jika perlu, durasi angiografi koroner dan PCI adalah 50,0 31,0 menit. Dalam 17 (22,4%) pasien, eptifibatide digunakan selama intervensi. Perangkat Angio-Seal digunakan di 26 (34,2%) pasien, dan enam (7,9%) menunjukkan komplikasi vaskular, seperti Hb-relevan perdarahan (6,6%) atau oklusi arteri (1,3%). Empat puluh satu (53,9%) pasien yang menerima langsung angiografi koroner setelah masuk rumah sakit bertahan sampai dikeluarkan dari rumah sakit (Tabel 1). Perbandingan pasien yang diobati dengan MTH dan pasien tidak dirawat dengan MTH 48 korban dari OHCA (63,2%) diobati dengan terapi hipotermia ringan setelah segera angiografi koroner, 28 pasien (36,8%) tidak. Dalam perbandingan kedua kelompok kami mengamati resusitasi lebih awam signifikan pada kelompok pasien yang tidak diobati dengan MTH (45,8% vs 75,0%; p = 0,01) dan komplikasi vaskular keseluruhan signifikan lebih pada kelompok pasien yang diobati dengan MTH (12,5% vs 0,0 %; p = 0,05). Tidak ada perbedaan yang signifikan dapat diamati dengan memperhatikan jenis kelamin patients`, usia, penangkapan menyaksikan, irama shockable awal, infark miokard, Int. J. Med. Sci. 2015, Vol. 12 http://www.medsci.org 308 prevalensi penyakit arteri koroner, PCI upaya, durasi angiografi koroner, penggunaan eptifibatide selama PCI, penggunaan Angio-Seal dan kelangsungan hidup sampai dikeluarkan dari rumah sakit (Tabel 1). Tabel 1: Karakteristik pasien dari semua pasien (kolom pertama), pasien yang diobati dengan terapi hipotermia ringan (MTH) berikut out-of-rumah sakit serangan jantung (OHCA; kolom kedua), dan korban OHCA yang tidak diobati dengan MTH (kolom ketiga) Semua pasien n = 76 Pasien yang diobati dengan MTH n = 48 Pasien tidak diobati dengan MTH n = 28 p jender laki 46 (60,5%) 29 (60,4%) 17 (60,7%) 0,98 Usia (tahun) [berbagai] 64,2 12,8 [ 34-88] 62,3 13,7 [34-88] 67,5 11,3 [47-88] 0.09 Disaksikan serangan jantung 60 (78,9%) 38 (79,2%) 22 (78,6%) 0,81 Lay resusitasi 43 (56,6%) 22 (45,8 %) 21 (75,0%) 0,01 Awal ritme shockable 44 (57,9%) 30 (62,5%) 14 (50,0%) 0,37 infark miokard 38 (50,0%) 25 (52,1%) 13 (46,4%) 0,92 ST elevasi infark miokard ( STEMI) 27 (35,5%) 19 (39,6%) 8 (28,6%) Non-ST elevasi infark miokard (NSTEMI) 11 (14,5%) 6 (12,5%) 5 (17,9%) penyakit arteri koroner 63 (82,9%) 40 (83,3%) 23 (82,1%) 0,89 Satu penyakit pembuluh 13 (17,1%) 7 (14,6%) 6 (21,4%) Dua penyakit pembuluh 17 (22,4%) 12 (25,0%) 5 (17,9%) penyakit Tiga kapal 33 (43,4%) 21 (43,8%) 12 (42,9%) Percutaneous coronary intervention (PCI) 53 (69,7%) 35 (72,9%) 18 (64,3%) 0,43 descendens anterior kiri (LAD) 21 (27,6%) 16 (33,3 %) 5 (17,9%) Ramus circumflexus (RCX) 7 (9,2%) 4 (8,3%) 3 (10,7%) arteri koroner kanan (RCA) 14 (18,4%) 8 (16,7%) 6 (21,4%) kapal multi Penyakit (MV) 10 (13,2%) 1 (1,3%) 6 (12,5%) 1 (2,1%) 4 (14,3%) 0 (0,0%) bypass arteri koroner graft (CABG) Penggunaan eptifibatide (Integrilin ) 17 ( 22,4%) 12 (25,0%) 5 (17,9%) 0,47 Lama angiografi koroner (min) [berbagai] 50,0 31,0 [7-186] 48,3 27,0 [8-132] 51,0 35,7 [7-186] 0.71 Vascular perangkat penutupan (Angio-Seal ) 26 (34,2%) 16 (33,3%) 10 (35,7%) 0,83 Vascular komplikasi 6 (7,9%) 6 (12,5%) 0 (0,0%) 0,05 Hb relevan pendarahan 5 (6,6%) 5 (10,4%) - 0,08 terapi konservatif 1 (1,3%) 1 (2,1%) - transfusi 3 (3,9%) 3 (6,3%) - Operasi + transfusi 1 (1,3%) 1 (2,1%) - Arteri oklusi 1 ( 1,3%) 1 (2,1%) - 0,44 operasi 1 (1,3%) 1 (2,1%) - Survival sampai dikeluarkan dari rumah sakit 41 (53,9%) 27 (56,3%) 14 (50,0%) 0,60 Perbandingan pasien yang diobati dengan MTH yang menerima Angio-Seal dan mereka yang tidak Pasien yang diobati dengan MTH dan menerima Angio-Seal disajikan kurang sering dengan infark miokard (31,3% berbanding 62,5%; p = 0,03), menerima kurang sering intervensi koroner perkutan (50,0% berbanding 84,4%; p = 0,01), diperlakukan dengan eptifibatide lebih jarang (6,25% dibandingkan 34,4%; p = 0,03), dan angiografi koroner lebih pendek (34,4 21,6 min vs 55,3 27,0 menit; p = 0,01) dibandingkan pasien yang tidak menerima perangkat Angio-Seal . Tidak ada perbedaan signifikan yang diamati berkaitan dengan pasien jenis kelamin, usia, penangkapan menyaksikan, lay-resusitasi, irama shockable awal, prevalensi penyakit arteri koroner, komplikasi vaskular, atau kelangsungan hidup sampai dikeluarkan dari rumah sakit (Tabel 2). Perbandingan pasien tidak dirawat dengan MTH yang menerima Angio-Seal dan mereka yang tidak Dalam korban yang menderita OHCA yang tidak diobati dengan MTH, tidak ada perbedaan yang bisa diamati antara pasien yang menerima Angio-Seal dan pasien yang tidak (Tabel 2). Diskusi hipotermia terapeutik Mild Dalam korban yang menderita OHCA, kombinasi MTH dan awal koroner angiografi PCI inklusif, jika perlu, telah digambarkan sebagai layak dan aman [2-6]. Secara khusus, komplikasi perdarahan telah dikeluarkan sebagai masalah klinis yang relevan terkait dengan MTH dalam beberapa penelitian sebelumnya [8-12]. Namun, tingkat pendarahan sangat bervariasi dalam studi yang berbeda. Sementara Nielsen et al. [2] dijelaskan peningkatan risiko perdarahan hanya 4% dari semua pasien berikut OHCA jika angiografi koroner dengan (6,2%) atau tanpa PCI (2,8%) dilakukan, penelitian lain melaporkan tingkat perdarahan lebih tinggi lebih dari 20% [6 , 13, 14] dan kecenderungan peningkatan komplikasi perdarahan pada kelompok MTH-diobati, yang kami juga diamati pada data kami (p = 0,08) (Tabel 2) [6, 14]. Mekanisme yang mendasari untuk pengamatan ini tidak diketahui. Koroner angiografi per se mempengaruhi koagulasi [15], dan hipotermia terapeutik mungkin, tergantung pada kedalaman dan durasi, menginduksi koagulopati [16]. Selain itu, dalam model hewan, thrombelastometry pada 34 C selama hipotermia menunjukkan perbedaan yang signifikan untuk waktu pembekuan dan pembentukan bekuan [17]. Namun demikian, untuk pengetahuan kita, tidak ada studi yang lebih lanjut bisa membedakan pengaruh masing-masing faktor individu. Selain itu, pasien secara rutin menerima heparin sebelum koroner angiografi dan platelet inhibitor dalam hubungan dengan PCI dalam dosis standar tanpa memandang status pasca-resusitasi mereka. Namun, meskipun dapat menunjukkan bahwa MTH tidak menambah penghambatan abciximab-diinduksi agregasi platelet [18], tidak ada laporan tentang pengaruh hipotermia pada konsentrasi clopidogrel, prasugrel, atau ticagrelor, dan risiko yang berpotensi mengakibatkan kurang atau overtreatment dengan obat ini pada korban OHCA diobati dengan MTH. Int. J. Med. Sci. 2015, Vol. 12 http://www.medsci.org 309 Tabel 2: Perbandingan serangan jantung out-of-rumah sakit (OHCA) korban yang menerima Angio-Seal setelah angiografi koroner dan orang-orang yang tidak menerima Angio-Seal dengan khusus memperhatikan perawatan tambahan Pasien hipotermia terapeutik ringan diobati dengan MTH Pasien tidak dirawat dengan MTH Angio-Seal n = 16 No Angio-Seal n = 32 p Angio-Seal n = 10 No Angio-Seal n = 18 p Pria jender 8 (50,0%) 21 (65,6%) 0,30 5 (50,0%) 12 (66,7%) 0,39 Usia (tahun) [berbagai] 66,0 14,6 [37-88] 60,4 13,0 [34-87] 0.19 66,8 15,4 [47-88] 67,9 8,7 [53-85] 0.81 Disaksikan serangan jantung 13 (81,3%) 25 (78,1%) 0,13 7 (70,0%) 15 (83,3%) 0,14 Lay resusitasi 6 (37,5%) 16 (50,0% ) 0.41 8 (80,0%) 13 (72,2%) 0,73 Awal ritme shockable 8 (50,0%) 22 (68,8%) 0,21 6 (60,0%) 8 (44,4%) 0,52 infark miokard 5 (31,3%) 20 (62,5%) 0.03 5 (50,0%) 8 (44,4%) 0,79 ST elevasi infark miokard 5 (31,3%) 14 (43,8%) 3 (30,0%) 5 (27,8%) (STEMI) 0 (0,0%) 6 (18,8%) 2 (20,0%) 3 (16,7%) Non-ST elevasi infark miokard (NSTEMI) penyakit arteri koroner 11 (68,8%) 29 (90,6%) 0,06 8 (80,0%) 15 (83,3%) 0,83 Satu penyakit pembuluh 2 (12,5% ) 5 (15,6%) 0 (0,0%) 6 (33,3%) Dua penyakit pembuluh 5 (31,3%) 7 (21,9%) 3 (30,0%) 2 (11,1%) Tiga penyakit pembuluh 4 (25,0%) 17 (53.1 %) 5 (50,0%) 7 (38,9%) intervensi koroner perkutan (PCI) 8 (50,0%) 27 (84,4%) 0,01 7 (70,0%) 11 (61,1%) 0,64 descendens anterior kiri (LAD) 4 (25,0% ) 12 (37,5%) 2 (20,0%) 3 (16,7%) Ramus circumflexus (RCX) 0 (0,0%) 4 (12,5%) 1 (10,0%) 2 (11,1%) arteri koroner kanan (RCA) 3 (18,8 %) 5 (15,6%) 1 (10,0%) 5 (27,8%) penyakit multi pembuluh (MV) 1 (6,3%) 5 (15,6%) 3 (30,0%) 1 (5,6%) bypass arteri koroner graft (CABG) 0 (0,0%) 1 (3,1%) 0 (0,0%) 0 (0,0%) Penggunaan eptifibatide (Integrilin ) 1 (6,3%) 11 (34,4%) 0,03 1 (10,0%) 4 (22,2%) 0.42 Durasi angiografi koroner (min) [berbagai] 34,4 21,6 [8-93] 55,3 27,0 [15-132] 0,01 58,5 54,4 [7-186] 46,8 20,2 [16-76] 0.42 Vascular komplikasi 3 (18,8 %) 3 (9,4%) 0,36 0 (0,0%) 0 (0,0%) na Hb perdarahan yang relevan 3 (18,8%) 2 (6,3%) 0,18 - - terapi konservatif 1 (6,3%) 0 (0,0%) - - transfusi 1 (6,3%) 2 (6,3%) - - Operasi 1 (6,3%) 0 (0,0%) - - Arteri oklusi 0 (0,0%) 1 (3,1%) 0,48 - - Operasi - 1 (3,1%) - - Survival sampai dikeluarkan dari rumah sakit 8 (50,0%) 19 (59,4%) 0,54 6 (60,0%) 8 (44,4%) 0,43 na: tidak tersedia Gambar 1: Perbedaan dalam kelompok pasien yang diobati dengan perangkat penutupan pembuluh darah tergantung pada apakah mereka menerima hipotermia ringan terapi (MTH) atau tidak. Int. J. Med. Sci. 2015, Vol. 12 http://www.medsci.org 310 Oleh karena itu kami merekomendasikan bahwa studi sebelumnya harus mencoba untuk memverifikasi apakah beberapa faktor dikombinasikan dapat meningkatkan risiko perdarahan, membutuhkan transfusi saat prosedur invasif dilakukan pada pasien diresusitasi diobati dengan MTH. Perangkat penutupan pembuluh darah Beberapa penelitian menggambarkan keamanan perangkat penutupan pembuluh darah setelah angiogram koroner rutin dan PCI rutin [19, 20], serta intervensi koroner berikut menggunakan antikoagulan dan GP IIb / IIIa inhibitor terapi [21]. Oleh karena itu, penggunaan VCD telah meningkat selama dekade terakhir, terutama karena penerapan VCD telah digambarkan sebagai independen terkait dengan penurunan tingkat komplikasi pembuluh darah dan panjang pasca-PCI tinggal di rumah sakit [22]. Namun demikian, ada juga data yang dilaporkan peningkatan risiko serius bagi perdarahan retroperitoneal pada pasien yang diobati dengan VCD [23]. Selain itu, berbeda dengan pengaturan elektif, risiko akses situs yang berhubungan dengan komplikasi vaskular meningkat secara signifikan setelah penerapan VCD Angio-Seal pada pasien yang menjalani catheterisations darurat untuk NSTEMI / STEMI bila dibandingkan dengan kompresi pengguna [24]. Sejak korban dari OHCA menjalani kateterisasi darurat, VCD harus digunakan dengan hati-hati dalam kelompok ini. Namun, tidak ada penelitian sebelumnya difokuskan secara khusus pada kolektif pasien ini. Dalam penelitian kami, VCD yang digunakan dalam sekitar sepertiga (34,2%) dari semua korban OHCA (Tabel 1). Analisis subkelompok lebih lanjut mengungkapkan bahwa, setidaknya pada pasien yang diobati dengan MTH, penerapan Angio-Seal perangkat dipengaruhi oleh temuan koroner, seperti infark miokard, intervensi koroner perkutan, atau pengobatan dengan GP IIb / IIIa inhibitor, dengan kurang sering digunakan VCD dalam prosedur yang lebih kompleks (Tabel 2). Namun, penggunaan VCD tidak disesuaikan untuk perawatan lebih lanjut dengan MTH secara umum (Tabel 2, Gambar 1). Terlepas dari apakah OHCA diobati dengan MTH setelah angiografi koroner atau tidak, kita tidak bisa mengamati perbedaan dalam tingkat komplikasi vaskular atau tingkat kelangsungan hidup antara pasien yang diobati dengan atau tanpa VCD (Tabel 2). Keterbatasan Penelitian ini adalah studi pusat tunggal dan, karena itu, temuan kami harus diverifikasi oleh penyelidikan lebih lanjut. Kesimpulan Dalam penelitian kami, tingkat keseluruhan komplikasi vaskular terkait dengan angiografi koroner lebih tinggi pada pasien yang diobati dengan MTH, tapi tidak terpengaruh oleh penerapan VCD. Oleh karena itu, data kami menunjukkan bahwa penggunaan VCD di korban OHCA mungkin juga layak dan aman pada pasien yang diobati dengan MTH, setidaknya jika keputusan untuk menggunakannya dengan hati-hati dipertimbangkan dan disesuaikan secara individual. 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