BACKGROUND: Surgery causes changes in hemostasis, leading to a hypercoagulable state. This postoperative increase in hemostatic function is attenuated in patients receiving regional anesthesia compared with those receiving general anesthesia. Regional anesthesia also decreases the neuroendocrine response to surgery compared with general anesthesia, and this effect is hypothesized to be responsible for the differences in hemostatis. To test the hypothesis that neuroendocrine hormones cause changes in hemostasis, we infused stress hormones into normal volunteers and measured hemostatic function. METHODS: After drug screening, 12 normal volunteers were studied. On two admissions, volunteers randomly received either stress hormone (epinephrine, cortisol, or glucagon) or placebo infusion for 24 h. During infusion, patients remained at bed rest and received controlled meals. Blood was obtained from indwelling venous catheters before infusion and 2, 8, and 24 h after the start of infusion. Blood was analyzed for neuroendocrine hormone concentrations, glucose, complete blood count, coagulation proteins, platelet reactivity, and activity of the fibrinolytic system. RESULTS: In the stress hormone group, concentrations of epinephrine, norepinephrine, cortisol, glucagon, and insulin were increased during the infusion period compared with those in the placebo group. Glucose concentrations and white blood cell counts were increased in the stress hormone group compared with those in the placebo group. Circulating fibrinogen concentrations increased 30% and ex vivo collagen-induced platelet reactivity increased 123% (aggregation) and 103% (dense granule release) in the stress hormone infusion group, whereas there was no change in the placebo group. Fibrinolytic proteins were similar in both groups, demonstrating a decrease in plasminogen activator inhibitor-1 activity at 8 and 24 h (196% in the hormone group vs. 199% in the placebo group). CONCLUSIONS: Infusion of stress hormones to concentrations found during surgery is safely tolerated and causes metabolic changes observed with surgery. Stress hormone infusion increases ex vivo platelet reactivity and fibrinogen concentrations that resemble changes seen postoperatively but does not recreate the postoperative decrease in fibrinolytic activity. Differences in neuroendocrine response between types of anesthesia may explain some postoperative changes in platelet function and acute phase reactivity, but additional uncharacterized factors are responsible for the differences in fibrinolysis.
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BACKGROUND: Surgery causes changes in hemostasis, leading to a hypercoagulable state. This postoperative increase in hemostatic function is attenuated in patients receiving regional anesthesia compared with those receiving general anesthesia. Regional anesthesia also decreases the neuroendocrine response to surgery compared with general anesthesia, and this effect is hypothesized to be responsible for the differences in hemostatis. To test the hypothesis that neuroendocrine hormones cause changes in hemostasis, we infused stress hormones into normal volunteers and measured hemostatic function. METHODS: After drug screening, 12 normal volunteers were studied. On two admissions, volunteers randomly received either stress hormone (epinephrine, cortisol, or glucagon) or placebo infusion for 24 h. During infusion, patients remained at bed rest and received controlled meals. Blood was obtained from indwelling venous catheters before infusion and 2, 8, and 24 h after the start of infusion. Blood was analyzed for neuroendocrine hormone concentrations, glucose, complete blood count, coagulation proteins, platelet reactivity, and activity of the fibrinolytic system. RESULTS: In the stress hormone group, concentrations of epinephrine, norepinephrine, cortisol, glucagon, and insulin were increased during the infusion period compared with those in the placebo group. Glucose concentrations and white blood cell counts were increased in the stress hormone group compared with those in the placebo group. Circulating fibrinogen concentrations increased 30% and ex vivo collagen-induced platelet reactivity increased 123% (aggregation) and 103% (dense granule release) in the stress hormone infusion group, whereas there was no change in the placebo group. Fibrinolytic proteins were similar in both groups, demonstrating a decrease in plasminogen activator inhibitor-1 activity at 8 and 24 h (196% in the hormone group vs. 199% in the placebo group). CONCLUSIONS: Infusion of stress hormones to concentrations found during surgery is safely tolerated and causes metabolic changes observed with surgery. Stress hormone infusion increases ex vivo platelet reactivity and fibrinogen concentrations that resemble changes seen postoperatively but does not recreate the postoperative decrease in fibrinolytic activity. Differences in neuroendocrine response between types of anesthesia may explain some postoperative changes in platelet function and acute phase reactivity, but additional uncharacterized factors are responsible for the differences in fibrinolysis.
Authors: Stefan Fischli; Viktor von Wyl; Walter Wuillemin; Roland von Känel; Philipp Schütz; Mirjam Christ-Crain; Fabian Studer; Lukas Brander; Guido Schüpfer; Jürg Metzger; Christoph Henzen Journal: J Endocr Soc Date: 2021-03-23