Background and ObjectivesA side effect to thoracic epidural anesthesia (TEA) is hypotension induced by central hypovolemia. This study addressed whether early activation (EA) versus late activation (LA) of TEA affects plasma pro-atrial natriuretic peptide (proANP) reflecting deviations in the central blood volume (CBV). We hypothesized that EA TEA would reduce plasma proANP, thus reflecting a decrease in CBV.MethodsA randomized, controlled, single-blinded trial was conducted. Patients undergoing open esophagectomy were randomized to EA (n=25, after induction of general anesthesia) or LA TEA (n=25, after re-established gastric continuity) with the epidural catheter placed at the interspaces Th7-8 or Th8-9. Plasma proANP was determined repetitively along with hemodynamic variables and administration of fluid/vasopressors as postoperative complications were noted.ResultsWith EA TEA, plasma proANP decreased following induction of anesthesia to the end of surgery (13%; 113±68 to 99±49 pmol/L; p=0.026), but that was not the case in the LA group (3%; 97±44 to 94±49 pmol/L; p=0.565) despite equal fluid balance (+1584±582 vs +1560±563 mL; p=0.888). Accordingly, the EA group required excessive treatment with vasopressors to maintain MAP >60 mm Hg during surgery (2.7±2 vs 1.6±1.4 ephedrine boluses; p=0.033 and infusion of phenylephrine for 216±86 vs 58±91 min; p<0.001). Plasma proANP and fluid balance were correlated only for EA patients (r=0.44; 95% CI 0.04 to 0.91; p=0.033).ConclusionsEA TEA reduces plasma proANP indicating that CBV becomes affected. Based on a correlation between plasma proANP and fluid balance, a 2000 mL volume surplus of lactated Ringer’s solution is required to maintain plasma proANP stable during open esophagectomy.Trial registration number2014-002036-14 (https://www.clinicaltrialsregister.eu/ctr-search/search?query=2014-002036-14).