Comparison of effects of no-, medium-, and high dose dexamethasone in adult cardiac surgery – A post-hoc analysis of the prospective, observational inflacor trial

Abstract

Introduction Since the introduction of cardiopulmonary bypass (CPB) patients suffered within the first postoperative days after cardiac surgery of systemic inflammatory response syndrome (SIRS). Patients discomfort and clinical symptoms of inflammation had been since target for prophylaxis and treatment with corticosteroids. High doses of corticosteroids to attenuate postoperative SIRS after CPB cardiac surgery are nowadays not recommended. This study compares the efficacy of low and high doses of dexamethasone. Methods Single center, prospective, observational study. Post-hoc analysis of n = 509 adult patients undergoing open heart surgery on CPB. Patients were grouped according to one dose of dexamethasone administered before CPB: I - none (n = 326), II - low dose - 0.4 mg/kg (n = 96), and III - high dose - 1.0 mg/kg (n = 87). Primary outcomes were: IL-6, ICAM1, soluble E-selectin levels three hours after operation, and CRP and WBC - 18 hours after operation. Secondary outcomes were: new-onset atrial fibrillation, myocardial infarction, delirium, sepsis, acute lung injury, acute kidney injury, length of stay in ICU and hospital, first-day drainage, and surgical reintervention. Stratified analyses were performed in CPB duration quartiles: 1: 11 – 100 Min. (n = 130), 2: 101-127 Min (n = 126), 3: 128-160 Min. (n = 126), 4: 161-476 Min. (n = 127). Results Dexamethasone ceased the trigger effect of CPB on levels of IL-6, ICAM1, sE-selectin at 3 hours after operation and CRP at 18 hours after operation. The levels of IL-6, soluble E-selectin, CRP and WBC didn't differ between groups II and III (p>0.05) and were lower than in group I (p<0.05). WBC count increase at 18 hours after operation was not related to CPB duration, but to dexamethasone dose alone (p<0.05). Primary outcome variables were in close association with the secondary outcomes: IL-6 was a predictor for ICU-LOS (p = 0.049) and AKI (p = 0.0001); ICAM1 for ICU-LOS (p = 0.047), AKI (p<0.0000), and sepsis (p = 0.005); CRP for AKI (p = 0.01) and increased chest drainage (p<0.0000); and WBC for AKI (p = 0.04) and sepsis (p = 0.0004). Significant effects of dexamethasone were found only in detailed stratified analyses: in the third CPB quartile MI prevalence was higher in group II, compared with group I or III. In patients within the third CPB quartile, group II had higher risk of postoperative MI (aRR = 2.15; p = 0.03) in comparison to group I. Higher delirium prevalence in group III when compared with group II was observed in the first CPB quartile (aRR = 7.19; p = 0.035). Incidence of surgical reintervention was significantly lower in groups II and III, regardless of the dose, in the 4th CPB quartile, when compared with group I. Discussion CPB duration is a surrogate for complexity of the surgical procedure. Therefore AKI, sepsis, and postoperative bleeding remained in correlation with CPB duration. Dexamethasone in a dose of 0.4 mg/kg was as effective as 1.0 mg/kg in attenuating post-operative SIRS parameters, but had no significant effect on early postoperative morbidity. Since the introduction of cardiopulmonary bypass (CPB) patients suffered within the first postoperative days after cardiac surgery of systemic inflammatory response syndrome (SIRS). Patients discomfort and clinical symptoms of inflammation had been since target for prophylaxis and treatment with corticosteroids. High doses of corticosteroids to attenuate postoperative SIRS after CPB cardiac surgery are nowadays not recommended. This study compares the efficacy of low and high doses of dexamethasone. Single center, prospective, observational study. Post-hoc analysis of n = 509 adult patients undergoing open heart surgery on CPB. Patients were grouped according to one dose of dexamethasone administered before CPB: I - none (n = 326), II - low dose - 0.4 mg/kg (n = 96), and III - high dose - 1.0 mg/kg (n = 87). Primary outcomes were: IL-6, ICAM1, soluble E-selectin levels three hours after operation, and CRP and WBC - 18 hours after operation. Secondary outcomes were: new-onset atrial fibrillation, myocardial infarction, delirium, sepsis, acute lung injury, acute kidney injury, length of stay in ICU and hospital, first-day drainage, and surgical reintervention. Stratified analyses were performed in CPB duration quartiles: 1: 11 – 100 Min. (n = 130), 2: 101-127 Min (n = 126), 3: 128-160 Min. (n = 126), 4: 161-476 Min. (n = 127). Dexamethasone ceased the trigger effect of CPB on levels of IL-6, ICAM1, sE-selectin at 3 hours after operation and CRP at 18 hours after operation. The levels of IL-6, soluble E-selectin, CRP and WBC didn't differ between groups II and III (p>0.05) and were lower than in group I (p<0.05). WBC count increase at 18 hours after operation was not related to CPB duration, but to dexamethasone dose alone (p<0.05). Primary outcome variables were in close association with the secondary outcomes: IL-6 was a predictor for ICU-LOS (p = 0.049) and AKI (p = 0.0001); ICAM1 for ICU-LOS (p = 0.047), AKI (p<0.0000), and sepsis (p = 0.005); CRP for AKI (p = 0.01) and increased chest drainage (p<0.0000); and WBC for AKI (p = 0.04) and sepsis (p = 0.0004). Significant effects of dexamethasone were found only in detailed stratified analyses: in the third CPB quartile MI prevalence was higher in group II, compared with group I or III. In patients within the third CPB quartile, group II had higher risk of postoperative MI (aRR = 2.15; p = 0.03) in comparison to group I. Higher delirium prevalence in group III when compared with group II was observed in the first CPB quartile (aRR = 7.19; p = 0.035). Incidence of surgical reintervention was significantly lower in groups II and III, regardless of the dose, in the 4th CPB quartile, when compared with group I. CPB duration is a surrogate for complexity of the surgical procedure. Therefore AKI, sepsis, and postoperative bleeding remained in correlation with CPB duration. Dexamethasone in a dose of 0.4 mg/kg was as effective as 1.0 mg/kg in attenuating post-operative SIRS parameters, but had no significant effect on early postoperative morbidity.