Abstract
Aims
Intravenous (IV) morphine has been shown to be independently associated with adverse clinical outcome in patients with non-STEMI. Currently, there are no data on the association of IV morphine and reperfusion success in STEMI. Thus, we thought to analyse the impact of IV morphine on ischemic injury and salvaged myocardium assessed by cardiac magnetic resonance imaging (CMR) in patients with STEMI reperfused by primary coronary intervention (PCI).
Methods and results
STEMI patients reperfused by primary PCI (n = 276) within 12 h after symptom onset underwent CMR 3 days after the index event [interquartile range (IQR) 2–4]. IV morphine administration was recorded in all patients. IV morphine was administered in 44.7 % (n = 123) of all patients. Patients in the IV morphine group displayed larger infarct size, higher extent of MO and lower myocardial salvage index (MSI) in comparison to the non-IV morphine group (all p < 0.05). In multivariable logistic regression analysis adjusted for TIMI-flow pre-PCI, time from symptom onset to PCI, Killip class and left ventricular ejection fraction, IV morphine was identified as an independent predictor for MSI <median (odds ratio 1.71, 95 % CI 1.02–2.87, p = 0.04).
Conclusion
In patients with STEMI, IV morphine administration prior to PCI is independently associated with suboptimal reperfusion success. These findings warrant randomised clinical trials assessing the effect of IV morphine on clinical outcome.
References
Steg PG, James SK, Atar D, Badano LP, Lundqvist CB, Borger MA, Di Mario C, Dickstein K, Ducrocq G, Fernandez-Aviles F, Gershlick AH, Giannuzzi P, Halvorsen S, Huber K, Juni P, Kastrati A, Knuuti J, Lenzen MJ, Mahaffey KW, Valgimigli M, Van’t Hof A, Widimsky P, Zahger D, Bax JJ, Baumgartner H, Ceconi C, Dean V, Deaton C, Fagard R, Funck-Brentano C, Hasdai D, Hoes A, Kirchhof P, Kolh P, McDonagh T, Moulin C, Popescu BA, Reiner Z, Sechtem U, Sirnes PA, Tendera M, Torbicki A, Vahanian A, Windecker S, Astin F, Astrom-Olsson K, Budaj A, Clemmensen P, Collet JP, Fox KA, Fuat A, Gustiene O, Hamm CW, Kala P, Lancellotti P, Maggioni AP, Merkely B, Neumann FJ, Piepoli MF, Van de Werf F, Verheugt F, Wallentin L (2012) ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: the task force on the management of ST-segment elevation acute myocardial infarction of the European Society of Cardiology (ESC). Eur Heart J 33(20):2569–2619. doi:10.1093/eurheartj/ehs215
Gross ER, Hsu AK, Gross GJ (2009) Acute methadone treatment reduces myocardial infarct size via the delta-opioid receptor in rats during reperfusion. Anesth Analg 109(5):1395–1402. doi:10.1213/ANE.0b013e3181b92201
Li R, Wong GT, Wong TM, Zhang Y, Xia Z, Irwin MG (2009) Intrathecal morphine preconditioning induces cardioprotection via activation of delta, kappa, and mu opioid receptors in rats. Anesth Analg 108(1):23–29. doi:10.1213/ane.0b013e3181884ba6
Amadesi S, Reni C, Katare R, Meloni M, Oikawa A, Beltrami AP, Avolio E, Cesselli D, Fortunato O, Spinetti G, Ascione R, Cangiano E, Valgimigli M, Hunt SP, Emanueli C, Madeddu P (2012) Role for substance p-based nociceptive signaling in progenitor cell activation and angiogenesis during ischemia in mice and in human subjects. Circulation 125 (14):1774–1786, S1–S19. doi:10.1161/CIRCULATIONAHA.111.089763
Balasubramanian S, Ramakrishnan S, Charboneau R, Wang J, Barke RA, Roy S (2001) Morphine sulfate inhibits hypoxia-induced vascular endothelial growth factor expression in endothelial cells and cardiac myocytes. J Mol Cell Cardiol 33(12):2179–2187. doi:10.1006/jmcc.2001.1480
Parodi G, Valenti R, Bellandi B, Migliorini A, Marcucci R, Comito V, Carrabba N, Santini A, Gensini GF, Abbate R, Antoniucci D (2013) Comparison of prasugrel and ticagrelor loading doses in ST-segment elevation myocardial infarction patients: RAPID (rapid activity of platelet inhibitor drugs) primary PCI study. J Am Coll Cardiol 61(15):1601–1606. doi:10.1016/j.jacc.2013.01.024
Hobl EL, Stimpfl T, Ebner J, Schoergenhofer C, Derhaschnig U, Sunder-Plassmann R, Jilma-Stohlawetz P, Mannhalter C, Posch M, Jilma B (2013) Morphine decreases clopidogrel concentrations and effects: a randomized, double blind, placebo-controlled trial. J Am Coll Cardiol. doi:10.1016/j.jacc.2013.10.068 (Epub ahead of print)
Meine TJ, Roe MT, Chen AY, Patel MR, Washam JB, Ohman EM, Peacock WF, Pollack CV Jr, Gibler WB, Peterson ED (2005) Association of intravenous morphine use and outcomes in acute coronary syndromes: results from the CRUSADE quality improvement initiative. Am Heart J 149(6):1043–1049. doi:10.1016/j.ahj.2005.02.010
Thiele H, Eitel I, Meinberg C, Desch S, Leuschner A, Pfeiffer D, Hartmann A, Lotze U, Strauss W, Schuler G (2011) Randomized comparison of pre-hospital-initiated facilitated percutaneous coronary intervention versus primary percutaneous coronary intervention in acute myocardial infarction very early after symptom onset: the LIPSIA-STEMI trial (Leipzig immediate prehospital facilitated angioplasty in ST-segment myocardial infarction). JACC Cardiovasc Interv 4(6):605–614. doi:10.1016/j.jcin.2011.01.013
Thiele H, Hildebrand L, Schirdewahn C, Eitel I, Adams V, Fuernau G, Erbs S, Linke A, Diederich KW, Nowak M, Desch S, Gutberlet M, Schuler G (2010) Impact of high-dose N-acetylcysteine versus placebo on contrast-induced nephropathy and myocardial reperfusion injury in unselected patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention. The LIPSIA-N-ACC (Prospective, Single-Blind, Placebo-Controlled, Randomized Leipzig Immediate PercutaneouS Coronary Intervention Acute Myocardial Infarction N-ACC) Trial. J Am Coll Cardiol 55(20):2201–2209. doi:10.1016/j.jacc.2009.08.091
Kwong R, Chan AK, Brown KA, Chan CW, Reynolds G, Tsang S, Davis RB (2006) Impact of unrecognized myocardial scar detected by cardiac magnetic resonance imaging on event-free survival in patients presenting without signs or symptoms of coronary artery disease. Circulation 113:2733–2743
Schroder R (2004) Prognostic impact of early ST-segment resolution in acute ST-elevation myocardial infarction. Circulation 110:e506–e510. doi:10.1161/01.CIR.0000147778.05979.E6
Killip T, Kimball JT (1967) Treatment of myocardial infarction in a coronary care unit. A two year experience with 250 patients. Am J Cardiol 20:457–464
TIMI Study Group (1985) The Thrombolysis in Myocardial Infarction (TIMI) trial: phase 1 findings. N Engl J Med 312:932–936. doi:10.1056/NEJM198504043121435
Kim HW, Farzaneh-Far A, Kim RJ (2009) Cardiovascular magnetic resonance in patients with myocardial infarction: current and emerging applications. J Am Coll Cardiol 55(1):1–16. doi:10.1016/j.jacc.2009.06.059
Friedrich MG, Abdel-Aty H, Taylor A, Schulz-Menger J, Messroghli D, Dietz R (2008) The salvaged area at risk in reperfused acute myocardial infarction as visualized by cardiovascular magnetic resonance. J Am Coll Cardiol 51(16):1581–1587
Thiele H, Kappl MJ, Conradi S, Niebauer J, Hambrecht R, Schuler G (2006) Reproducibility of chronic and acute infarct size measurement by delayed enhancement magnetic resonance imaging. J Am Coll Cardiol 47(8):1641–1645. doi:10.1016/j.jacc.2005.11.065
Desch S, Engelhardt H, Meissner J, Eitel I, Sareban M, Fuernau G, de Waha S, Grothoff M, Gutberlet M, Schuler G, Thiele H (2011) Reliability of myocardial salvage assessment by cardiac magnetic resonance imaging in acute reperfused myocardial infarction. Int J Cardiovasc Imaging 28(2):263–272. doi:10.1007/s10554-011-9802-9
Rouby JJ, Eurin B, Glaser P, Guillosson JJ, Nafziger J, Guesde R, Viars P (1981) Hemodynamic and metabolic effects of morphine in the critically ill. Circulation 64(1):53–59
Rochitte CE, Lima JAC, Bluemke DA, Reeder SB, McVeigh ER, Furuta T, Becker LC, Melin JA (1998) Magnitude and time course of microvascular obstruction and tissue injury after acute myocardial infarction. Circulation 98:1006–1014
Kim RJ, Fieno DS, Parrish TB, Harris K, Chen EL, Simonetti O, Bundy J, Finn JP, Klocke FJ, Judd RM (1999) Relationship of MRI delayed contrast enhancement to irreversible injury, infarct age, and contractile function. Circulation 100(19):1992–2002
de Waha S, Desch S, Eitel I, Fuernau G, Zachrau J, Leuschner A, Zachrau J, Schuler G, Thiele H (2010) Impact of early versus late microvascular obstruction assessed by magnetic resonance imaging on long-term outcome after ST-elevation myocardial infarction—a comparison to traditional prognostic markers. Eur Heart J 31(21):2660–2668. doi:10.1093/eurheartj/ehq247
Eitel I, Desch S, Fuernau G, Hildebrand L, Gutberlet M, Schuler G, Thiele H (2010) Prognostic significance and determinants of myocardial salvage assessed by cardiovascular magnetic resonance in acute reperfused myocardial infarction. J Am Coll Cardiol 55(22):2470–2479. doi:10.1016/j.jacc.2010.01.049
Hombach V, Grebe O, Merkle N, Waldenmaier S, Hoher M, Kochs M, Wohrle J, Kestler HA (2005) Sequelae of acute myocardial infarction regarding cardiac structure and function and their prognostic significance as assessed by magnetic resonance imaging. Eur Heart J 26(6):549–557. doi:10.1093/eurheartj/ehi147
Acknowledgments
We gratefully acknowledge our colleagues from the Department of Diagnostic and Interventional Radiology at the University Leipzig, Heart Centre supporting CMR image acquisition.
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On behalf of all the authors, the corresponding author states that there is no conflict of interest.
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de Waha, S., Eitel, I., Desch, S. et al. Intravenous morphine administration and reperfusion success in ST-elevation myocardial infarction: insights from cardiac magnetic resonance imaging. Clin Res Cardiol 104, 727–734 (2015). https://doi.org/10.1007/s00392-015-0835-2
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DOI: https://doi.org/10.1007/s00392-015-0835-2