Remote ischaemic preconditioning on gene expression and circulating proteins after subacute laparoscopic cholecystectomy: randomized clinical trial.

BACKGROUND: Surgical stress may lead to postsurgical hypercoagulability, endothelial dysfunction and systemic inflammation, which can impact on patient recovery. Remote ischaemic preconditioning is a procedure that activates the body's endogenous defences against ischaemia and reperfusion injury. Studies have suggested that remote ischaemic preconditioning has antithrombotic, antioxidative and anti-inflammatory effects. The hypothesis was that remote ischaemic preconditioning reduces surgery-induced systemic stress response. METHOD: During a 24-month period (2019-2021), adult patients undergoing subacute laparoscopic cholecystectomy due to acute cholecystitis were randomized to remote ischaemic preconditioning or control. Remote ischaemic preconditioning was performed less than 4 h before surgery on the upper arm. It consisted of four cycles of 5 min ischaemia and 5 min reperfusion. The gene expression of 750 genes involved in inflammatory processes, oxidative stress and endothelial function was investigated preoperatively and 2-4 h after surgery in both groups. In addition, changes in 20 inflammation- and vascular trauma-associated proteins were assessed preoperatively, 2-4 h after surgery and 24 h after surgery. RESULTS: A total of 60 patients were randomized. There were no statistically significant differences in gene expression 2-4 h after surgery between the groups (P > 0.05). Remote ischaemic preconditioning did not affect concentrations of circulating proteins up to 24 h after surgery (P > 0.05). CONCLUSION: The study did not demonstrate any effect of remote ischaemic preconditioning on expression levels of the chosen genes or in circulating immunological cytokines and vascular trauma-associated proteins up to 24 h after subacute laparoscopic cholecystectomy in patients with acute cholecystitis.

Effect of Remote Ischaemic Preconditioning on Perioperative Endothelial Dysfunction in Non-Cardiac Surgery: A Randomised Clinical Trial.

Endothelial dysfunction result from inflammation and excessive production of reactive oxygen species as part of the surgical stress response. Remote ischemic preconditioning (RIPC) potentially exerts anti-oxidative and anti-inflammatory properties, which might stabilise the endothelial function after non-cardiac surgery. This was a single centre randomised clinical trial including 60 patients undergoing sub-acute laparoscopic cholecystectomy due to acute cholecystitis. Patients were randomised to RIPC or control. The RIPC procedure consisted of four cycles of five minutes of ischaemia and reperfusion of one upper extremity. Endothelial function was assessed as the reactive hyperaemia index (RHI) and circulating biomarkers of nitric oxide (NO) bioavailability (L-arginine, asymmetric dimethylarginine (ADMA), L-arginine/ADMA ratio, tetra- and dihydrobiopterin (BH4 and BH2), and total plasma biopterin) preoperative, 2-4 h after surgery and 24 h after surgery. RHI did not differ between the groups (p = 0.07). Neither did levels of circulating biomarkers of NO bioavailability change in response to RIPC. L-arginine and L-arginine/ADMA ratio was suppressed preoperatively and increased 24 h after surgery (p < 0.001). The BH4/BH2-ratio had a high preoperative level, decreased 2-4 h after surgery and remained low 24 h after surgery (p = 0.01). RIPC did not influence endothelial function or markers of NO bioavailability until 24 h after sub-acute laparoscopic cholecystectomy. In response to surgery, markers of NO bioavailability increased, and oxidative stress decreased. These findings support that a minimally invasive removal of the inflamed gallbladder countereffects reduced markers of NO bioavailability and increased oxidative stress caused by acute cholecystitis.

Glycemic profile and quality of recovery after emergency abdominal surgery-A prospective explorative cohort study.

Associations between degrees of postoperative hyperglycemia and morbidity has previously been established. There may be an association between the glycemic profile and patient-reported recovery, and this may be a target for perioperative quality improvements. We aimed to investigate the association between metrics of the 30-day glycemic profile and patient-reported recovery in nondiabetic patients after major abdominal surgery. In a prospective, explorative cohort study, nondiabetic adult patients undergoing acute, major abdominal surgery were included within 24 h after surgery. Interstitial fluid glucose concentration was measured for 30 consecutive days with a continuous glucose measurement device. The validated questionnaire 'Quality of Recovery-15' was used to assess patient-reported quality of recovery on postoperative days 10, 20, and 30. Follow-up time was divided into five-day postoperative intervals using days 26-30 as a reference. Linear mixed models were applied to investigate temporal changes in mean p-glucose, coefficient of variation, time within 70-140 mg/dl, and time above 200 mg/dl in relation to patient-reported recovery. Twenty-seven patients completed the study per protocol. A hyperglycemic event (>200 mg/dl) occurred in 18 of 27 patients (67%) within the first three postoperative days. Compared to the reference period, the coefficient of variation was significantly increased during all time intervals, indicating prolonged postoperative insulin resistance. During 30 days of follow-up, patient-reported recovery was associated with the coefficient of variation measured for 3 and 5 days before the corresponding recovery score assessment (recovery score estimate -1.52 [p < .001] and -0.92 [p = .006], respectively). We did not find an association between the remaining metrics and patient-reported recovery. Alterations in the glycemic profile are frequent and prolonged during the first postoperative month after major surgery probably due to peripheral insulin resistance. Our findings indicate that high-glycemic variation is associated with poorer patient-reported recovery and might represent a proxy for care improvements in the postoperative period.