Cyclohexanone contamination from extracorporeal circuits impairs cardiovascular function

Abstract

Extracorporeal circulation provides critical life support in the face of cardiopulmonary or renal failure, but it also introduces a host of unique morbidities characterized by edema formation, cardiac insufficiency, autonomic dysfunction, and altered vasomotor function. We tested the hypothesis that cyclohexanone (CHX), a solvent used in production of extracorporeal circuits and intravenous (IV) bags, leaches into the contained fluids and can replicate these clinical morbidities. Crystalloid fluid samples from circuits and IV bags were analyzed by gas chromatography-mass spectrometry to provide a range of clinical CHX exposure levels, revealing CHX contamination of sampled fluids (9.63-3,694 g/l). In vivo rat studies were conducted (n ϭ 49) to investigate the effects of a bolus IV infusion of CHX vs. saline alone on cardiovascular function, baroreflex responsiveness, and edema formation. Cardiovascular function was evaluated by cardiac output, heart rate, stroke volume, vascular resistance, arterial pressure, and ventricular contractility. Baroreflex function was assessed by mean femoral arterial pressure responses to bilateral carotid occlusion. Edema formation was assessed by the ratio of wet to dry organ weights for lungs, liver, kidneys, and skin. CHX infusion led to systemic hypotension; pulmonary hypertension; depressed contractility, heart rate, stroke volume, and cardiac output; and elevated vascular resistance (P Ͻ 0.05). Mean arterial pressure responsiveness to carotid occlusion was dampened after CHX infusion (from ϩ17.25 Ϯ 1.8 to ϩ5.61 Ϯ 3.2 mmHg; P Ͻ 0.05). CHX infusion led to significantly higher wet-to-dry weight ratios vs. saline only (3.8 Ϯ 0.06 vs. 3.5 Ϯ 0.05; P Ͻ 0.05). CHX can reproduce clinical cardiovascular, neurological, and edema morbidities associated with extracorporeal circulatory treatment. ventricular contractility; autonomic nervous system; vasoconstriction; edema EXTRACORPOREAL CIRCULATION [EC; cardiopulmonary bypass, extracorporeal membrane oxygenation (ECMO), hemodialysis, hemofiltration] has become a primary tool in hospitals, providing critical life support in the face of cardiopulmonary or renal failure. However, EC also introduces a host of unique morbidities, including labile blood pressure, depressed cardiac output, ventricular dysfunction, arrhythmias, and major organ edema (1-2, 8, 17-19, 22, 31-33, 40). Although several randomized clinical trials have been conducted to minimize these and other effects of EC treatment (17), EC morbidity rates still remain high and represent a significant barrier to improved patient care, as evidenced by increased time in the intensive care unit (ICU) and on inotropic support.Cyclohexanone [CHX; C 6 H 10 (AO)] is an organic solvent used in the production of polyvinyl chloride (PVC) medical devices, including intravenous (IV) fluid bags and EC circuits. CHX easily migrates from PVC tubing and connections into fluids that come in contact with PVC (10, 12, 35, 37), irrespective of the type of IV fluid. CHX can leach from PVC bags and IV tub...

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