EComment. Potential therapeutic agents in vasoplegic syndrome after cardiac surgery

Abstract

Vasoplegic syndrome (VS) or vasodilatory shock frequently occurs after cardiac surgery, particularly with cardiopulmonary bypass(CPB). It is often associated with high morbidity and mortality, especially if it is resistant to intravascular volume expansion and conventional vasoconstrictive drugs [1]. This complication is similar to septic shock and characterized by severe and persistent hypotension, decreased systemic vascular resistance (SVR), normal or increased cardiac output (CO), low intra-cardiac filling pressures, and the necessity for high-dose catecholamines. Until today, the aetiology of VS is not fully understood. However, this syndrome is thought to be caused by the inflammatory-mediated dysregulation of endothelium homeostasis and subsequent endothelial dysfunction, including endothelial cell activation, endothelial permeability augmentation, coagulation defects, production of different regulators, and vascular tone disorders [1]. We read with great interest the paper by Kortekaas et al [2]. The authors report that pre-existing endothelial cell activation, reflected by higher baseline von Willebrand factor pro-peptide and soluble P-selectin levels is a predisposing factor for VS after mitral valve surgery. They also conclude that this activation may have resulted in desensibilization of endothelium in patients with VS. We would like to add some comments on possible agents for the management of VS VS is attributed to a combination of endothelial injury, arginine-vasopressin system dysfunction, and the release of vasodilatory inflammatory mediators[1]. Although these markers may be useful for the identification of patients at increased risk of developing VS, effective treatment strategies for this syndrome are currently lacking. The choice of vasoconstrictive agents for VS is a matter of controversy. To maintain adequate haemodynamics for VS, the conventional treatment based on fluid resuscitation and catecholamine drugs is ineffective in a subset of patients with profound vasodilatation[1]. Arginine vasopressin (AVP) and methylene blue (MB) may be used as additional rescue or a preventative treatment for VS [1, 3]. AVP is well-known to treat norepinephrine-resistant vasodilatation but may be associated rebound hypotension after discontinuation [3,4]. AVP significantly increases mean arterial pressure (MAP) and SVR, and results in a marked decrease in norepinephrine doses [1]. Tayama and associates [3] treated postoperative refractory low SVR hypotension concomitant with pulmonary hypertension by AVP. They reported that exogenous AVP normalized SVR and increased MAP. They also observed that AVP enhanced urine output and improved respiratory function. Noto and co-workers [4] reported that they treated six patients with terlipressin (TP; 1 mg bolus), a synthetic analogue of AVP for post-CPB refractory vasodilatory hypotension. In these patients, the authors suggested that exogenous TP administration normalized SVR and increased MAP with a minimum effect on pulmonary pressure. MB, an inhibitor of nitric oxide synthase and guanylate cyclase, seems to be a possible effective therapeutical option and to improve outcomes in patients with catecholamine-resistant VS after cardiac surgery [1, 5]. In a prospective observational study, Leyh and colleagues [5] tested the effect of MB (2 mg/kg over 20 minutes) in 54 patients with norepinephrine-resistant VS. In this study, MAP increased and norepinephrine dose decreased 1 hour after MB administration. These changes were accompanied by a significant decrease in CO. Finally, we think that further studies are necessary to find the most appropriate possible therapeutic agents for VS. Conflict of interest: none declared