Impact of high-dose glucocorticoid on endothelial damage after liver resection - a double-blinded randomized substudy.

OBJECTIVES: Postoperative endothelial damage potentially results in increased vascular leakage, tissue edema and subsequent complications. The preventive effect of glucocorticoids on endothelial damage after surgery is sparsely described, including the relation between endothelial damage and the postoperative inflammatory response. Thus, we aimed to assess the preventive effect of high-dose glucocorticoids on postoperative endothelial damage, and the association between endothelial damage and inflammation after surgery. METHODS: This was a predefined substudy of a randomized double-blinded clinical trial of methylprednisolone 10 mg/kg (high dose) vs. dexamethasone 8 mg (low dose) in patients undergoing liver resection at Rigshospitalet, Copenhagen. In total 25 patients undergoing major liver resection (11 in the high-dose group and 14 in the low-dose group) were included. The primary outcome was changed in five endothelial biomarkers and the secondary outcome was changes in inflammation [C-reactive protein (CRP)] for the first three postoperative days. RESULTS: No statistically significant difference was found for any endothelial biomarkers postoperatively between the two groups (P > 0.15, for all). High-dose glucocorticoids significantly reduced CRP on day 3 compared to low-dose glucocorticoids [median difference on a postoperative day 3, 59.6 g/L, (84.2; 27.1), P < 0.002]. No significant correlation between endothelial damage and CRP levels was seen. CONCLUSIONS: No significant effect of high- vs. low-dose glucocorticoids on development in endothelial biomarkers after major liver resection was observed. High-dose glucocorticoids reduce the inflammatory response though without correlation to endothelial damage. Future studies should assess the clinical impact of increased endothelial biomarkers for clinical perioperative outcomes.

Impact of high-dose glucocorticoid on endothelial damage after liver resection - a double-blinded randomized substudy.

OBJECTIVES: Postoperative endothelial damage potentially results in increased vascular leakage, tissue edema and subsequent complications. The preventive effect of glucocorticoids on endothelial damage after surgery is sparsely described, including the relation between endothelial damage and the postoperative inflammatory response. Thus, we aimed to assess the preventive effect of high-dose glucocorticoids on postoperative endothelial damage, and the association between endothelial damage and inflammation after surgery. METHODS: This was a predefined substudy of a randomized double-blinded clinical trial of methylprednisolone 10 mg/kg (high dose) vs. dexamethasone 8 mg (low dose) in patients undergoing liver resection at Rigshospitalet, Copenhagen. In total 25 patients undergoing major liver resection (11 in the high-dose group and 14 in the low-dose group) were included. The primary outcome was changed in five endothelial biomarkers and the secondary outcome was changes in inflammation [C-reactive protein (CRP)] for the first three postoperative days. RESULTS: No statistically significant difference was found for any endothelial biomarkers postoperatively between the two groups (P > 0.15, for all). High-dose glucocorticoids significantly reduced CRP on day 3 compared to low-dose glucocorticoids [median difference on a postoperative day 3, 59.6 g/L, (84.2; 27.1), P < 0.002]. No significant correlation between endothelial damage and CRP levels was seen. CONCLUSIONS: No significant effect of high- vs. low-dose glucocorticoids on development in endothelial biomarkers after major liver resection was observed. High-dose glucocorticoids reduce the inflammatory response though without correlation to endothelial damage. Future studies should assess the clinical impact of increased endothelial biomarkers for clinical perioperative outcomes.

Preoperative TruCulture® whole blood cytokine response predicts post-operative inflammation in pancreaticoduodenectomy patients-A pilot cohort study.

Major surgery is associated with substantial morbidity and mortality with early post-operative adverse events (POAE) occurring in 30% of patients within the first 30 days. The underlying pathogenesis is multifactorial, including immune dysfunction and increased inflammatory response to surgery. We investigated preoperative immune function by the TruCulture® whole blood technique in a cohort of patients undergoing pancreaticoduodenectomy (PD), hypothesizing that patients developing inflammatory POAE defined as leucocytosis, fever or high (above median) area under the curve (AUC) C-reactive protein (CRP) the first post-operative week would display perturbed preoperative immune function. Sixty-two adult patients were screened, 30 included and 11 excluded post-inclusion due to other surgical procedures than PD and post-operative complications directly attributed to surgery, leaving 19 patients for analysis of preoperative immune function. Patients developing leucocytosis (n = 5, 26%) had lower Toll-like receptor (TLR)-3-stimulated IL-12p40 and higher Candida Albicans (TLR1/2/4/6, Dectin-1)-stimulated TNF-α, compared to patients without leucocytosis (all P < .05). Patients developing fever (n = 7, 37%) had lower TLR7/8-stimulated IFN-γ and patients with high AUC CRP (n = 9, 47%) had lower TLR3-stimulated IFN-γ and IL-6 and lower TLR7/8-stimulated IL-10 (all P < .05), compared to patients without fever or low CRP, respectively. In conclusion, patients with inflammatory POAE displayed lower preoperative stimulated IL-12p40, IFN-γ, IL-6 and IL-10 and higher TNF-α response, compared to patients without inflammatory POAE. This finding suggests that TruCulture is a feasible immunologic screening tool in surgical patients, with a potential for preoperative identification of patients at increased risk for inflammatory POAE, allowing for risk-based intervention trials.

Persistent severe post-operative hypotension after pancreaticoduodenectomy is related to increased inflammatory response.

BACKGROUND: Hypotension during major surgery is frequent, resulting in increased need for observation in the post-anaesthesia care unit and treatment including vasopressors and fluids. However, although severe hypotension in the immediate post-operative recovery phase after major surgery is suggested to be related to increased morbidity and mortality, the underlying risk factors are not well described, hindering advancements in prevention and treatment. METHODS: We performed a retrospective study assessing factors (age, gender, body-mass index, cardiac co-morbidity, haemoglobin, absolute and increase in c-reactive protein on the first post-operative day, bleeding, fluid balance at the end of surgery and the first post-operative day) related to severe persistent hypotension (SPH) (SPH: need for noradrenaline to maintain a mean arterial blood pressure (MAP) >65.0 mm Hg on the morning after surgery) and occurrence of other early (24 hours) complications. One hundred patients undergoing pancreaticoduodenectomy (PD) with pre-operative high-dose glucocorticoid and goal-directed fluid therapy were enrolled and perioperative data collected from anaesthetic and medical records. RESULTS: Forty-five patients had SPH, who had a significantly higher increase in CRP levels the morning after surgery (median 50 mg L-1 vs 41 mg L-1 , SPH vs non-SPH, respectively, P = .028), and a significantly more positive fluid balance at discharge (median 1457 ml vs 1031 ml, respectively, P = .027) vs patients without SPH. CONCLUSIONS: Severe persistent hypotension after PD was associated with significantly increased inflammatory response and increased need for fluids. Future studies should investigate the effect of further inflammatory control in PD to improve haemodynamics and morbidity.