• Christian Koch, Emmanuel Schneck, Christoph Arens, Melanie Markmann, Michael Sander, Michael Henrich, Markus A Weigand, and Christoph Lichtenstern.
• Department of Anesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital of Giessen and Marburg, Rudolf-Buchheim-Strasse 7, 35392, Giessen, Germany. Christian.Koch@chiru.med.uni-giessen.de.
• Int J Clin Pharm. 2020 Feb 1; 42 (1): 72-79.

AbstractBackground Echinocandins are well-established agents for the treatment of patients with fungal infections, but growing evidence questions their safety in special patient populations prone to systemic inflammatory responses. Objective The study aimed to analyse early hemodynamic changes during echinocandin therapy in critically ill surgical patients. Setting The study was conducted at the surgical intensive care unit at the University Hospital of Giessen, Germany. Methods This single-centre retrospective study includes data from critically ill patients who underwent primary antifungal treatment during 2009-2013. Main outcome measures Hemodynamic parameters, need for vasopressor/inotropic therapy, and dose of vasopressor/inotropic therapy were recorded 2 h before and 2 h after the onset of antifungal treatment. Comparisons of echinocandins to azoles and analysis of a combined endpoint (decrease of mean arterial pressure  ≥ 10 mmHg and/or new or increased dosages of norepinephrine, epinephrine, or dobutamine) were performed. Results We found 342 episodes of intravenous antifungal treatment (33 [9.6%] anidulafungin, 116 [33.9%] caspofungin, 132 [38.6%] fluconazole, 17 [5%] micafungin, 44 [12.9%] voriconazole). Group comparisons revealed no significant differences of hemodynamic parameters, need for vasopressor/inotropic therapy, and dose of vasopressor/inotropic therapy, expect for a decreased dose of norepinephrine in the fluconazole group (p < 0.001). The combined endpoint occurred in 58 (50%) caspofungin-, 16 (48.5%) anidulafungin-, 4 (23.5%) micafungin-, 23 (17.4%) fluconazole-, and 15 (34.1%) voriconazole treatment episodes. Secondary analysis of the combined anidulafungin/caspofungin group to the azoles group (fluconazole, voriconazole) showed a significant decrease of  mean arterial pressure ≥ 10 mmHg (n = 37 [25%] vs. n = 27 [15%], OR = 1.8, p = 0.04), increased use of norepinephrine (n = 38 [26%] vs. n = 12 [7%], OR = 4.7, p ≤ 0.001), increased use of dobutamine (n = 12 [8%] vs. n = 4 [2%], OR = 3.8, p = 0.02), and the combined endpoint (n = 74 [50%] vs. n = 38 [21%], OR = 3.6, p ≤ 0.001). Conclusion Our retrospective data might demonstrate clinically relevant hemodynamic-depressing effects of anidulafungin and caspofungin. Further prospective acquisition of clinical data will be necessary to evaluate their impact on hemodynamic function.

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