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.

Early postoperative recovery after peri-acetabular osteotomy: A double-blind, randomised single-centre trial of 48 vs. 8 mg dexamethasone.

BACKGROUND: Peri-acetabular osteotomy is the joint-preserving treatment of choice in young adults with hip dysplasia but is associated with intense pain and high opioid consumption postoperatively. OBJECTIVES: To investigate whether 48 mg of pre-operative dexamethasone was superior to a standard dose of 8 mg on reducing pain in the immediate postoperative phase. DESIGN: A randomised, double-blind trial. SETTING: Single-centre, primary facility. May 2017 to August 2019. PATIENTS: At least 18 years undergoing peri-acetabular osteotomy. INTERVENTIONS: Patients were randomised 1 : 1 to 48 or 8 mg dexamethasone intravenous (i.v.) as a single pre-operative injection. All patients received a standardised peri-operative protocol, including pre-operative acetaminophen and gabapentin, total i.v. anaesthesia and local anaesthetic catheter based wound administration. MAIN OUTCOME MEASURE: Number of patients with moderate/severe pain [>3 on a numeric rating scale (NRS)] in the immediate postoperative phase. RESULTS: Sixty-four patients (32 in each group) were included, and their data analysed. At some point from tracheal extubation until transfer to the ward, the NRS was more than 3 in 75% (24/32) of the 48 mg group and in 66% (21/32) in the 8 mg group, odds ratio 1.571 (95% CI, 0.552 to 4.64), P = 0.585. Patients in the 48 mg group received less opioid [cumulative rescue analgesics, oral morphine equivalents (OMEQ)] during postoperative days 0-4: median [IQR] OMEQ was 36 [15 to 85] mg vs. 79 [36 to 154] mg in the 48 and 8 mg group, respectively, P = 0.034. There were no statistically significant differences regarding complications, rate of infections or readmissions. CONCLUSION: Forty-eight milligram of dexamethasone did not reduce pain in the immediate postoperative phase compared with an 8 mg dose. We observed insignificantly lower pain scores and significantly lower cumulated opioid requirements in the 48 mg group during the first four postoperative days. TRIAL REGISTRATION: Clinicaltrials.gov, NCT03161938, EudraCT (2017-000544-1).

Surgical stress response and the potential role of preoperative glucocorticoids on post-anesthesia care unit recovery.

The immediate postoperative course in the post-anesthesia care unit (PACU) remains a challenge across surgical procedures. Postoperative pain, sedation/cognitive dysfunction, nausea and vomiting (PONV), circulatory and respiratory problems and orthostatic intolerance constitute the bulk of the difficulties that may delay the postoperative recovery. A common feature in the observed organ dysfunctions is the inflammatory response to surgery during the acute postoperative recovery phase, suggesting that control of inflammation may improve outcomes and reduce complications. This narrative review focuses on our understanding of the inflammatory responses in the acute PACU setting in relation to organ dysfunction and suggests where further research is warranted. The main finding is that current evidence suggests inflammation to potentially impair on almost all organ dysfunctions observed in the post-anesthesia care unit (PACU), but with a scarcity of intervention studies using glucocorticoids to control inflammation. We, therefore, suggest a future research focus on the role of inflammation and effect of glucocorticoids in the PACU setting to improve patient recovery.

National variation in transfusion strategies in patients with upper gastrointestinal bleeding.

INTRODUCTION: An optimal transfusion strategy for patients with upper gastrointestinal bleeding (UGIB) has yet to be established. The national guidelines contain recommendations for patients with life-threating bleeding in general, but no specific recommendations for patients with UGIB. We hypothesised that there are variations in transfusion strategies for patients with UGIB across the Danish regions. METHODS: We performed a retrospective, register-based, analysis on transfusions given to all patients with non-variceal UGIB in Denmark in 2011-2013. We compared the results from the five regions in Denmark in order to discover regional differences. RESULTS: A total of 5,292 admissions with treatment for non-variceal UGIB were identified, and analysis was made for the total group and a massive transfusions group (330 admissions). In the Capital Region, transfusion of platelets was more likely than in any other region for all patients (p < 0.01) including the massive transfusion group (p = 0.03). In the North Region, transfusion of fresh frozen plasma was more likely for the massive transfusion group (p = 0.01). CONCLUSION: The observed differences warrant further prospective cohort studies in order to provide a foundation for transfusion recommendations for patients with UGIB. FUNDING: none. TRIAL REGISTRATION: not relevant.